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Fulltext Combined protein- and nucleic acid-level effects of rs1143679 (R77H), a lupus-predisposing variant within ITGAM

Maiti AK, Kim-Howard X, Motghare P, Pradhan V, Chua KH, Sun C, et al.

Hum Mol Genet, 2014 Aug 1;23(15):4161-76.
PMID: 24608226 DOI: 10.1093/hmg/ddu106

Integrin alpha M (ITGAM; CD11b) is a component of the macrophage-1 antigen complex, which mediates leukocyte adhesion, migration and phagocytosis as part of the immune system. We previously identified a missense polymorphism, rs1143679 (R77H), strongly associated with systemic lupus erythematosus (SLE). However, the molecular mechanisms of this variant are incompletely understood. A meta-analysis of published and novel data on 28 439 individuals with European, African, Hispanic and Asian ancestries reinforces genetic association between rs1143679 and SLE [Pmeta = 3.60 × 10(-90), odds ratio (OR) = 1.76]. Since rs1143679 is in the most active region of chromatin regulation and transcription factor binding in ITGAM, we quantitated ITGAM RNA and surface protein levels in monocytes from patients with each rs1143679 genotype. We observed that transcript levels significantly decreased for the risk allele ('A') relative to the non-risk allele ('G'), in a dose-dependent fashion: ('AA' < 'AG' < 'GG'). CD11b protein levels in patients' monocytes were directly correlated with RNA levels. Strikingly, heterozygous individuals express much lower (average 10- to 15-fold reduction) amounts of the 'A' transcript than 'G' transcript. We found that the non-risk sequence surrounding rs1143679 exhibits transcriptional enhancer activity in vivo and binds to Ku70/80, NFKB1 and EBF1 in vitro, functions that are significantly reduced with the risk allele. Mutant CD11b protein shows significantly reduced binding to fibrinogen and vitronectin, relative to non-risk, both in purified protein and in cellular models. This two-pronged contribution (nucleic acid- and protein-level) of the rs1143679 risk allele to decreasing ITGAM activity provides insight into the molecular mechanisms of its potent association with SLE.

Matched MeSH terms: Monocytes/metabolism*; Monocytes/pathology
Cryptotanshinone attenuates in vitro oxLDL-induced pre-lesional atherosclerotic events

Ang KP, Tan HK, Selvaraja M, Kadir AA, Somchit MN, Akim AM, et al.

Planta Med, 2011 Nov;77(16):1782-7.
PMID: 21614753 DOI: 10.1055/s-0030-1271119

Development of early stage atherosclerosis involves the activation of endothelial cells by oxidized low-density lipoprotein (oxLDL) with subsequent increases in endothelial permeability and expression of adhesion molecules favoring the adherence of monocytes to the endothelium. Cryptotanshinone (CTS), a major compound derived from the Chinese herb Salvia miltiorrhiza, is known for its protective effects against cardiovascular diseases. The aim of this study was to determine whether CTS could prevent the oxLDL-induced early atherosclerotic events. OxLDL (100 µg/mL) was used to increase endothelial permeability and induce monocyte-endothelial cell adhesion in human umbilical vein endothelial cells (HUVECs). Endothelial nitric oxide (NO) concentrations, a permeability-regulating molecule, and expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were measured. Results show that a) endothelial hyperpermeability was suppressed by 94 % (p

Matched MeSH terms: Monocytes/drug effects; Monocytes/physiology
1'-Acetoxychavicol acetate inhibits NLRP3-dependent inflammasome activation via mitochondrial ROS suppression

Sok SPM, Ori D, Wada A, Okude H, Kawasaki T, Momota M, et al.

Int Immunol, 2021 06 18;33(7):373-386.
PMID: 33830232 DOI: 10.1093/intimm/dxab016

The nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing (NLRP) 3 inflammasome is a multiprotein complex that triggers Caspase-1-mediated IL-1β production and pyroptosis, and its dysregulation is associated with the pathogenesis of inflammatory diseases. 1'-Acetoxychavicol acetate (ACA) is a natural compound in the rhizome of tropical ginger Alpinia species with anti-microbial, anti-allergic and anti-cancer properties. In this study, we found that ACA suppressed NLRP3 inflammasome activation in mouse bone marrow-derived macrophages and human THP-1 monocytes. ACA inhibited Caspase-1 activation and IL-1β production by NLRP3 agonists such as nigericin, monosodium urate (MSU) crystals, and ATP. Moreover, it suppressed oligomerization of the adapter molecule, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1-mediated cleavage of pyroptosis executor Gasdermin D. Mechanistically, ACA inhibited generation of mitochondrial reactive oxygen species (ROS) and prevented release of oxidized mitochondrial DNA, which trigger NLRP3 inflammasome activation. ACA also prevented NLRP3 inflammasome activation in vivo, as evidenced in the MSU crystal-induced peritonitis and dextran sodium sulfate-induced colitis mouse models accompanied by decreased Caspase-1 activation. Thus, ACA is a potent inhibitor of the NLRP3 inflammasome for prevention of NLRP3-associated inflammatory diseases.

Matched MeSH terms: Monocytes/drug effects; Monocytes/metabolism
Fulltext Long non-coding RNA expression in primary human monocytes

Mirsafian H, Manda SS, Mitchell CJ, Sreenivasamurthy S, Ripen AM, Mohamad SB, et al.

Genomics, 2016 07;108(1):37-45.
PMID: 26778813 DOI: 10.1016/j.ygeno.2016.01.002

Long non-coding RNAs (lncRNAs) have been shown to possess a wide range of functions in both cellular and developmental processes including cancers. Although some of the lncRNAs have been implicated in the regulation of the immune response, the exact function of the large majority of lncRNAs still remains unknown. In this study, we characterized the lncRNAs in human primary monocytes, an essential component of the innate immune system. We performed RNA sequencing of monocytes from four individuals and combined our data with eleven other publicly available datasets. Our analysis led to identification of ~8000 lncRNAs of which >1000 have not been previously reported in monocytes. PCR-based validation of a subset of the identified novel long intergenic noncoding RNAs (lincRNAs) revealed distinct expression patterns. Our study provides a landscape of lncRNAs in monocytes, which could facilitate future experimental studies to characterize the functions of these molecules in the innate immune system.

Matched MeSH terms: Monocytes/metabolism*
Fulltext Aberrant monocyte responses predict and characterize dengue virus infection in individuals with severe disease

Yong YK, Tan HY, Jen SH, Shankar EM, Natkunam SK, Sathar J, et al.

J Transl Med, 2017 05 31;15(1):121.
PMID: 28569153 DOI: 10.1186/s12967-017-1226-4

BACKGROUND: Currently, several assays can diagnose acute dengue infection. However, none of these assays can predict the severity of the disease. Biomarkers that predicts the likelihood that a dengue patient will develop a severe form of the disease could permit more efficient patient triage and allows better supportive care for the individual in need, especially during dengue outbreaks.
METHODS: We measured 20 plasma markers i.e. IFN-γ, IL-10, granzyme-B, CX3CL1, IP-10, RANTES, CXCL8, CXCL6, VCAM, ICAM, VEGF, HGF, sCD25, IL-18, LBP, sCD14, sCD163, MIF, MCP-1 and MIP-1β in 141 dengue patients in over 230 specimens and correlate the levels of these plasma markers with the development of dengue without warning signs (DWS-), dengue with warning signs (DWS+) and severe dengue (SD).
RESULTS: Our results show that the elevation of plasma levels of IL-18 at both febrile and defervescence phase was significantly associated with DWS+ and SD; whilst increase of sCD14 and LBP at febrile phase were associated with severity of dengue disease. By using receiver operating characteristic (ROC) analysis, the IL-18, LBP and sCD14 were significantly predicted the development of more severe form of dengue disease (DWS+/SD) (AUC = 0.768, P

Matched MeSH terms: Monocytes/cytology*
Survival and immunomodulation of stem cells from human extracted deciduous teeth expanded in pooled human and foetal bovine sera

Haque N, Khan IM, Abu Kasim NH

Cytokine, 2019 08;120:144-154.
PMID: 31071675 DOI: 10.1016/j.cyto.2019.04.018

The immunomodulatory properties of mesenchymal stem cells (MSCs) from autologous and allogeneic sources are useful in stimulating tissue regeneration and repair. To obtain a high number of MSCs for transplantation requires extensive in vitro expansion with culture media supplements that can cause xeno-contamination of cells potentially compromising function and clinical outcomes. In this study stem cells from human extracted deciduous teeth (SHED) were cultured in Knockout™ DMEM supplemented with either pooled human serum (pHS) or foetal bovine serum (FBS) to compare their suitability in maintaining immunomodulatory properties of cells during in vitro expansion. No significant difference in cell survival of SHED grown in pHS (pHS-SHED) or FBS (FBS-SHED) was observed when co-cultured with complement, monocytes or lymphocytes. However, significant changes in the expression of sixteen paracrine factors involved in immunomodulation were observed in the supernatants of FBS-SHED co-cultures with monocytes or lymphocytes compared to that in pHS-SHEDs after both 24 and 120 h of incubation. Further analysis of changing protein levels of paracrine factors in co-cultures using biological pathway analysis software predicted upregulation of functions associated with immunogenicity in FBS-SHED and lymphocyte co-cultures compared to pHS-SHED co-cultures. Pathway analysis also predicted significant stimulation of HMGB1 and TREM1 signalling pathways in FBS-SHED co-cultures indicating activation of immune cells and inflammation. Though FBS supplementation does not impact survival of SHED, our combinatorial biological pathway analysis supports the idea that in vitro expansion of SHEDs in pHS provides optimal conditions to minimise xeno-contamination and inflammation and maintain their immunomodulatory properties.

Matched MeSH terms: Monocytes/cytology
Fulltext Review of the Long-term Effects of Autologous Bone-Marrow Mononuclear Cell Implantation on Clinical Outcomes in Patients with Critical Limb Ischemia

Yusoff FM, Kajikawa M, Matsui S, Hashimoto H, Kishimoto S, Maruhashi T, et al.

Sci Rep, 2019 05 22;9(1):7711.
PMID: 31118440 DOI: 10.1038/s41598-019-44176-5

Critical limb ischemia (CLI) is associated with a high risk of limb amputation. It has been shown that cell therapy is safe and has beneficial effects on ischemic clinical symptoms in patients with CLI. The aim of this study was to further investigate the outcomes of intramuscular injection of autologous bone-marrow mononuclear cells (BM-MNCs) in a long-term follow-up period in atherosclerotic peripheral arterial disease (PAD) patients who have no optional therapy. This study was a retrospective and observational study that was carried out to evaluate long-term clinical outcomes in 42 lower limbs of 30 patients with atherosclerotic PAD who underwent BM-MNC implantation. The median follow-up period was 9.25 (range, 6-16) years. The overall amputation-free rates were 73.0% at 5 years after BM-MNC implantation and 70.4% at 10 years in patients with atherosclerotic PAD. The overall amputation-free rates at 5 years and at 10 years after implantation of BM-MNCs were significantly higher in atherosclerotic PAD patients than in internal controls and historical controls. There were no significant differences in amputation rates between the internal control group and historical control group. The rate of overall survival was not significantly different between the BM-MNC implantation group and the historical control group. Implantation of autologous BM-MNCs is feasible for a long-term follow-up period in patients with CLI who have no optional therapy.

Matched MeSH terms: Monocytes/transplantation*
Fulltext A pathogenic role for tumor necrosis factor-related apoptosis-inducing ligand in chronic obstructive pulmonary disease

Haw TJ, Starkey MR, Nair PM, Pavlidis S, Liu G, Nguyen DH, et al.

Mucosal Immunol, 2016 Jul;9(4):859-72.
PMID: 26555706 DOI: 10.1038/mi.2015.111

Chronic obstructive pulmonary disease (COPD) is a life-threatening inflammatory respiratory disorder, often induced by cigarette smoke (CS) exposure. The development of effective therapies is impaired by a lack of understanding of the underlining mechanisms. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with inflammatory and apoptotic properties. We interrogated a mouse model of CS-induced experimental COPD and human tissues to identify a novel role for TRAIL in COPD pathogenesis. CS exposure of wild-type mice increased TRAIL and its receptor messenger RNA (mRNA) expression and protein levels, as well as the number of TRAIL(+)CD11b(+) monocytes in the lung. TRAIL and its receptor mRNA were also increased in human COPD. CS-exposed TRAIL-deficient mice had decreased pulmonary inflammation, pro-inflammatory mediators, emphysema-like alveolar enlargement, and improved lung function. TRAIL-deficient mice also developed spontaneous small airway changes with increased epithelial cell thickness and collagen deposition, independent of CS exposure. Importantly, therapeutic neutralization of TRAIL, after the establishment of early-stage experimental COPD, reduced pulmonary inflammation, emphysema-like alveolar enlargement, and small airway changes. These data provide further evidence for TRAIL being a pivotal inflammatory factor in respiratory diseases, and the first preclinical evidence to suggest that therapeutic agents that target TRAIL may be effective in COPD therapy.

Matched MeSH terms: Monocytes/immunology*
Fulltext Molecular investigation of feline coronavirus (FCOV) in local pet cats

Hoong, L.W., Yasmin, A.R., Mummoorthy, K., Arshad, S.S., Omar, A.R., Anand, P., et al.

Jurnal Veterinar Malaysia, 2019;31(2):13-18.
MyJurnal

Feline coronavirus (FCoV) infection is a very common in cat population. FCoV is further classified into two biotypes namely feline enteric coronavirus (FECV) and mutated feline infectious peritonitis virus (FIPV), in which FIPV causes a fatal immune complex disease by changing the tropism from enterocytes to monocytes. Previous studies on molecular detection of FCoV in cats were carried out in catteries but limited study investigate the presence of FCoV antigen in local pet cats. By considering this fact, this study aims to detect FCoV antigen via RT-PCR assay in local pet cats and to compare the similarity of the identified FCoV strain with previous related virus by phylogenetic analysis. By using convenience sampling, rectal swabs and buffy coat were collected from 16 clinically ill pet cats and 5 healthy pet cats. Viral RNA was extracted and subjected to one-step RT-PCR, targeting polymerase gene. Only one out of 21 fecal samples was positive for FCoV and none from buffy coat samples. Phylogenetic analysis revealed that the identified positive sample was highly homologous, up to 95%, to FCoV strain from Netherlands and South Korea on partial sequence of polymerase gene. In conclusion, this study detected FCoV antigen in local pet cats from fecal samples while negative detection from fecal and buffy coat samples could not completely rule out the possibilities of FCoV infection due to the complexity of the virus diagnosis that require multiple series of analysis.

Matched MeSH terms: Monocytes
Piper sarmentosum attenuates TNF-α-induced VCAM-1 and ICAM-1 expression in human umbilical vein endothelial cells

Ismail SM, Sundar UM, Hui CK, Aminuddin A, Ugusman A

J Taibah Univ Med Sci, 2018 Jun;13(3):225-231.
PMID: 31435328 DOI: 10.1016/j.jtumed.2018.01.003

Objectives: Inflammation plays a key role in the pathogenesis of atherosclerosis. Piper sarmentosum is an herb with antioxidant and anti-atherosclerotic activities. The aim of this study was to evaluate the anti-inflammatory properties of an aqueous extract of P. sarmentosum (AEPS) in human umbilical vein endothelial cells (HUVECs).
Methods: HUVECs were divided into six groups: control, treatment with 10 ng/ml TNF-α, and co-treatment of 10 ng/ml TNF-α with four different concentrations of AEPS (100, 150, 250, and 300 μg/ml) for 24 h. Subsequently, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) protein expression, U937 monocyte cells adhesion, and nuclear factor-kappaB (NF-κB) p65 expression in HUVECs were measured.
Results: Treatment of TNF-α-stimulated HUVECs with AEPS at different concentrations resulted in decreased VCAM-1 and ICAM-1 protein expression in a dose-dependent manner. Furthermore, AEPS also inhibited TNF-α-stimulated U937 monocyte cells adhesion to HUVECs. In addition, AEPS reduced TNF-α-induced NF-κB p65 expression in a dose-dependent manner.
Conclusions: The results indicated that AEPS suppressed TNF-α-induced VCAM-1 and ICAM-1 expression NF-κB signaling.

Matched MeSH terms: Monocytes
Fulltext PH-responsive strontium nanoparticles for targeted gene therapy against mammary carcinoma cells

Bakhtiar A, Chowdhury EH

Asian J Pharm Sci, 2021 Mar;16(2):236-252.
PMID: 33995617 DOI: 10.1016/j.ajps.2020.11.002

Genetic intervention via the delivery of functional genes such as plasmid DNA (pDNA) and short-interfering RNA (siRNA) offers a great way to treat many single or multiple genetic defects effectively, including mammary carcinoma. Delivery of naked therapeutic genes or siRNAs is, however, short-lived due to biological clearance by scavenging nucleases and circulating monocytes. Low cellular internalization of negatively-charged nucleic acids further causes low transfection or silencing activity. Development of safe and effectual gene vectors is therefore undeniably crucial to the success of nucleic acid delivery. Inorganic nanoparticles have attracted considerable attention in the recent years due to their high loading capacity and encapsulation activity. Here we introduce strontium salt-based nanoparticles, namely, strontium sulfate, strontium sulfite and strontium fluoride as new inorganic nanocarriers. Generated strontium salt particles were found to be nanosized with high affinity towards negatively-charged pDNA and siRNA. Degradation of the particles was seen with a drop in pH, suggesting their capacity to respond to pH change and undergo dissolution at endosomal pH to release the genetic materials. While the particles are relatively nontoxic towards the cells, siRNA-loaded SrF2 and SrSO3 particles exerted superior transgene expression and knockdown activity of MAPK and AKT, leading to inhibition of their phosphorylation to a distinctive extent in both MCF-7 and 4T1 cells. Strontium salt nanoparticles have thus emerged as a promising tool for applications in cancer gene therapy.

Matched MeSH terms: Monocytes
Fulltext Immunofluorescence (IF) pattern, autoantigens of anti-neutrophil cytoplasmic antibodies (ANCA) and their clinical associations

Masita Arip, Marlyn Mohammad, Salbiah Nawi, Shahnaz Murad

Jurnal Sains Kesihatan Malaysia, 2010;8(2):37-41.
MyJurnal

Antineutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against primary granules of neutrophils and monocytes' lysosomes. In general, c-ANCA is strongly associated with vasculitic disorders mainly in ANCA-associated systemic vasculitis (AASV). p-ANCA have been identified in several diseases such as primary (AASV) and secondary vasculitis such as collagen vascular diseases, rheumatoid arthritis and inflammatory bowel diseases given the term 'ANCA-associated disease.' The objective of this study was to determine the rate of ANCA positivity by indirect immunofluorescent (IF) and enzyme linked immunosorbent assay (ELISA) and its association with AASV and ANCA associated diseases. Serum from patients with history suspicion of systemic vasculitis were tested for ANCA by IF. Those samples positive for ANCA by IF were further tested for antibodies against myeloperoxidase (MPO) and proteinase 3 (PR3) using the ELISA. Clinical data from medical records were obtained and analyzed. Of 468 samples, a total of 110 were positive for ANCA by IF. IF results showed a p-ANCA pattern in 96 patients and c-ANCA in 14. Of 110 IF positive ANCA, 45 patients were positive by ELISA. Seventeen were positive for MPO-ANCA, 9 were PR3-ANCA positive and 19 were both MPO and PR3 positive. Only 2 patients were classified AASV ie Wegener granulomatosis and the other with microscopic polyangiitis. The remaining patients (n = 108) may be classified as ANCA associated diseases. Our study showed that pANCA (87.3%) was the more common ANCA pattern and 40.9% of IF positive samples were positive for PR3- and MPOANCA.

Matched MeSH terms: Monocytes
Nipah Virus Infection of Immature Dendritic Cells Increases Its Transendothelial Migration Across Human Brain Microvascular Endothelial Cells

Tiong V, Shu MH, Wong WF, AbuBakar S, Chang LY

Front Microbiol, 2018;9:2747.
PMID: 30483242 DOI: 10.3389/fmicb.2018.02747

Nipah virus (NiV) can infect multiple organs in humans with the central nervous system (CNS) being the most severely affected. Currently, it is not fully understood how NiV spreads throughout the body. NiV has been shown to infect certain leukocyte populations and we hypothesized that these infected cells could cross the blood-brain barrier (BBB), facilitating NiV entry into the CNS. Here, three leukocyte types, primary immature dendritic cells (iDC), primary monocytes (pMO), and monocytic cell line (THP-1), were evaluated for permissiveness to NiV. We found only iDC and THP-1 were permissive to NiV. Transendothelial migration of mock-infected and NiV-infected leukocytes was then evaluated using an in vitro BBB model established with human brain microvascular endothelial cells (HBMEC). There was approximately a threefold increase in migration of NiV-infected iDC across endothelial monolayer when compared to mock-infected iDC. In contrast, migration rates for pMO and THP-1 did not change upon NiV infection. Across TNF-α-treated endothelial monolayer, there was significant increase of almost twofold in migration of NiV-infected iDC and THP-1 over mock-infected cells. Immunofluorescence analysis showed the migrated NiV-infected leukocytes retained their ability to infect other cells. This study demonstrates for the first time that active NiV infection of iDC and THP-1 increased their transendothelial migration activity across HBMEC and activation of HBMEC by TNF-α further promoted migration. The findings suggest that NiV infection of leukocytes to disseminate the virus via the "Trojan horse" mechanism is a viable route of entry into the CNS.

Matched MeSH terms: Monocytes
Fulltext Ficus deltoidea suppresses endothelial activation, inflammation, monocytes adhesion and oxidative stress via NF-κB and eNOS pathways in stimulated human coronary artery endothelial cells

Mohd Ariff A, Abu Bakar NA, Abd Muid S, Omar E, Ismail NH, Ali AM, et al.

BMC Complement Med Ther, 2020 Feb 17;20(1):56.
PMID: 32066426 DOI: 10.1186/s12906-020-2844-6

BACKGROUND: Ficus deltoidea (FD) has been shown to have antidiabetic, anti-inflammatory, antinociceptive and antioxidant properties. However, its effects on key events in the pathogenesis of atherosclerosis are unknown.
AIM: To investigate the endothelial activation, inflammation, monocyte-endothelial cell binding and oxidative stress effects of four FD varieties.
METHODS: Human coronary artery endothelial cells (HCAEC) were incubated with different concentrations of aqueous ethanolic extracts of FD var. trengganuensis (FDT), var. kunstleri (FDK), var. deltoidea (FDD) and var. intermedia (FDI), together with LPS. Protein and gene expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), endothelial-leukocyte adhesion molecule-1 (E-selectin), interleukin-6 (IL-6), Nuclear factor-κB (NF-κB) p50 and p65 and endothelial nitric oxide synthase (eNOS) were measured using ELISA and QuantiGene plex, respectively. Adhesion of monocyte to HCAEC and formation of reactive oxygen species (ROS) were detected by Rose Bengal staining and 2'-7'-dichlorofluorescein diacetate (DCFH-DA) assay.
RESULTS: FDK exhibited the highest inhibition of biomarkers in relation to endothelial activation and inflammation, second in reducing monocyte binding (17.3%) compared to other varieties. FDK (25.6%) was also the most potent at decreasing ROS production.
CONCLUSION: FD has anti-atherogenic effects, possibly mediated by NF-κB and eNOS pathways; with FDK being the most potent variety. It is potentially beneficial in mitigating atherogenesis.

Matched MeSH terms: Monocytes
Peripheral blood CD163(+) monocytes and soluble CD163 in dry and neovascular age-related macular degeneration

Daftarian N, Zandi S, Piryaie G, Nikougoftar Zarif M, Ranaei Pirmardan E, Yamaguchi M, et al.

FASEB J, 2020 Jun;34(6):8001-8011.
PMID: 32333612 DOI: 10.1096/fj.201901902RR

Macrophages are the main infiltrating immune cells in choroidal neovascularization (CNV), a hallmark of the human wet, or neovascular age-related macular degeneration (AMD). Due to their plasticity and ability to adapt to the local microenvironment in a tissue-dependent manner, macrophages display polar functional phenotypes characterized by their cell surface markers and their cytokine profiles. We found accumulation of hemoglobin-scavenging cluster of differentiation 163 (CD163)(+) macrophages in laser-induced CNV lesions and higher expression of CD163(+) monocytes in the peripheral blood on day 7 post injury in mice. In comparison, CD80(+) macrophages did not differ with laser-injury in young or aged mice and did not significantly change in the peripheral blood of CNV mice. We examined the percentages of CD163(+), CD206(+), and CD80(+) monocytes in the peripheral blood of patients with wet AMD, patients with dry AMD, and in age-matched individuals without AMD as controls. Percentages of peripheral blood CD163(+) monocytes in both dry AMD (P

Matched MeSH terms: Monocytes
Fulltext Elements of the complete blood count associated with cardiovascular disease incidence: Findings from the EPIC-NL cohort study

Lassale C, Curtis A, Abete I, van der Schouw YT, Verschuren WMM, Lu Y, et al.

Sci Rep, 2018 02 19;8(1):3290.
PMID: 29459661 DOI: 10.1038/s41598-018-21661-x

All blood cells (white blood cells [WBC], red blood cells [RBC] and platelets) can play a role in atherosclerosis. Complete blood count (CBC) is widely available in clinical practice but utility as potential risk factors for cardiovascular disease (CVD) is uncertain. Our aim was to assess the associations of pre-diagnostic CBC with incidence of CVD in 14,362 adults free of CVD and aged 47.8 (±11.7) years at baseline, followed-up for 11.4 years (992 incident cases). Cox proportional hazards regressions were used to estimate HRs and 95%CI. Comparing the top (T3) to bottom (T1) tertile, increased total WBC, lymphocyte, monocyte and neutrophil counts were associated with higher CVD risk: 1.31 (1.10; 1.55), 1.20 (1.02; 1.41), 1.21 (1.03; 1.41) and 1.24 (1.05; 1.47), as well as mean corpuscular volume (MCV: 1.23 [1.04; 1.46]) and red cell distribution width (RDW: 1.22 [1.03; 1.44]). Platelets displayed an association for count values above the clinically normal range: 1.49 (1.00; 2.22). To conclude, total and differential WBC count, MCV, RDW and platelet count likely play a role in the aetiology of CVD but only WBC provide a modest improvement for the prediction of 10-year CVD risk over traditional CVD risk factors in a general population.

Matched MeSH terms: Monocytes
Omega-3 fatty acids and leukocyte-endothelium adhesion: Novel anti-atherosclerotic actions

Baker EJ, Yusof MH, Yaqoob P, Miles EA, Calder PC

Mol Aspects Med, 2018 12;64:169-181.
PMID: 30102930 DOI: 10.1016/j.mam.2018.08.002

Endothelial cells (ECs) play a role in the optimal function of blood vessels. When endothelial function becomes dysregulated, the risk of developing atherosclerosis increases. Specifically, upregulation of adhesion molecule expression on ECs promotes the movement of leukocytes, particularly monocytes, into the vessel wall. Here, monocytes differentiate into macrophages and may become foam cells, contributing to the initiation and progression of an atherosclerotic plaque. The ability of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) to influence the expression of adhesion molecules by ECs and to modulate leukocyte-endothelial adhesion has been studied in cell culture using various types of ECs, in animal feeding studies and in human trials; the latter have tended to evaluate soluble forms of adhesion molecules that circulate in the bloodstream. These studies indicate that n-3 PUFAs (both eicosapentaenoic acid and docosahexaenoic acid) can decrease the expression of key adhesion molecules, such as vascular cell adhesion molecule 1, by ECs and that this results in decreased adhesive interactions between leukocytes and ECs. These findings suggest that n-3 PUFAs may lower leukocyte infiltration into the vascular wall, which could contribute to reduced atherosclerosis and lowered risk of cardiovascular disease.

Matched MeSH terms: Monocytes
The effects of a synthetic curcuminoid analogue, 2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone on proinflammatory signaling pathways and CLP-induced lethal sepsis in mice

Tham CL, Lam KW, Rajajendram R, Cheah YK, Sulaiman MR, Lajis NH, et al.

Eur J Pharmacol, 2011 Feb 10;652(1-3):136-44.
PMID: 21114991 DOI: 10.1016/j.ejphar.2010.10.092

We previously showed that 2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone (BHMC), suppressed the synthesis of various proinflammatory mediators. In this study we explain the mechanism of action of BHMC in lipopolysaccharide (LPS)-induced U937 monocytes and further show that BHMC prevents lethality of CLP-induced sepsis. BHMC showed dose-dependent inhibitory effects on p38, JNK and ERK 1/2 activity as determined by inhibition of phosphorylation of downstream transcription factors ATF-2, c-Jun and Elk-1 respectively. Inhibition of these transcription factors subsequently caused total abolishment of AP-1-DNA binding. BHMC inhibited p65 NF-κB nuclear translocation and DNA binding of p65 NF-κB only at the highest concentration used (12.5μM) but failed to alter phosphorylation of JNK, ERK1/2 and STAT-1. Since the inhibition of p38 activity was more pronounced we evaluated the possibility that BHMC may bind to p38. Molecular docking experiments confirmed that BHMC fits well in the highly conserved hydrophobic pocket of p38 MAP kinase. We also show that BHMC was able to improve survival from lethal sepsis in a murine caecal-ligation and puncture (CLP) model.

Matched MeSH terms: Monocytes/metabolism
Fulltext A case report of adult T-cell leukaemia/lymphoma

Shanmugam H, Eow GI, Nadarajan VS

Malays J Pathol, 2009 Jun;31(1):63-6.
PMID: 19694316 MyJurnal

Adult T-cell leukaemia/lymphoma (ATLL) is a rare T lymphoproliferative disorder which is aetiologically linked with human T-cell lymphotropic virus type-1 (HTLV-1). HTLV-1 is endemic in Japan, Caribbean and Africa. The highest incidence of ATLL is in Japan although sporadic cases have been reported elsewhere in the world. We describe a case of ATLL with an unusual presentation which we believe is the first reported case of ATLL in Malaysia based on our literature search. A 51-year-old Indian lady was referred to University Malaya Medical Centre for an incidental finding of lymphocytosis while being investigated for pallor and giddiness. Clinical examination revealed bilateral shotty cervical lymph nodes with no hepato-splenomegaly or skin lesions. Laboratory investigations showed absolute lymphocytosis (38 x 10(9)/L) with a mildly increased serum lactate dehydrogenase. The peripheral blood smear showed the presence of predominantly small to medium sized, non-flower lymphocytes. The bone marrow showed similar findings of prominent lymphocytosis. Immunophenotyping of the bone marrow mononuclear cells showed CD3+, CD4+, CD5+, CD7- and CD25+ which is characteristic of ATLL phenotype. HTLV-1 infection was confirmed by the presence of HTLV-1 proviral DNA in the tumor cells using conventional Polymerase Chain Reaction (PCR) and real-time PCR. Here, we discuss the pathogenesis and characteristics of ATLL as well as the detection of HTLV-1 by real time PCR.

Matched MeSH terms: Monocytes/pathology
Fulltext Genetic polymorphisms in the CD14 gene are associated with monocyte activation and carotid intima-media thickness in HIV-infected patients on antiretroviral therapy

Yong YK, Shankar EM, Westhorpe CL, Maisa A, Spelman T, Kamarulzaman A, et al.

Medicine (Baltimore), 2016 Aug;95(31):e4477.
PMID: 27495090 DOI: 10.1097/MD.0000000000004477

HIV-infected individuals on antiretroviral therapy (ART) are at increased risk of cardiovascular disease (CVD). Given the relationship between innate immune activation and CVD, we investigated the association of single-nucleotide polymorphisms (SNPs) in TLR4 and CD14 and carotid intima-media thickness (cIMT), a surrogate measurement for CVD, in HIV-infected individuals on ART and HIV-uninfected controls as a cross-sectional, case-control study. We quantified the frequency of monocyte subsets (CD14, CD16), markers of monocyte activation (CD38, HLA-DR), and endothelial adhesion (CCR2, CX3CR1, CD11b) by flow cytometry. Plasma levels of lipopolysaccharide, sCD163, sCD14, sCX3CL1, and sCCL2, were measured by ELISA. Genotyping of TLR4 and CD14 SNPs was also performed. The TT genotype for CD14/-260SNP but not the CC/CT genotype was associated with elevated plasma sCD14, and increased frequency of CD11b+CD14+ monocytes in HIV-infected individuals. The TT genotype was associated with lower cIMT in HIV-infected patients (n = 47) but not in HIV-uninfected controls (n = 37). The AG genotype for TLR4/+896 was associated with increased CX3CR1 expression on total monocytes among HIV-infected individuals and increased sCCL2 and fibrinogen levels in HIV-uninfected controls. SNPs in CD14/-260 and TLR4/+896 were significantly associated with different markers of systemic and monocyte activation and cIMT that differed between HIV-infected participants on ART and HIV-uninfected controls. Further investigation on the relationship of these SNPs with a clinical endpoint of CVD is warranted in HIV-infected patients on ART.

Matched MeSH terms: Monocytes/metabolism*

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