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We did not find any association between receiving a PI-containing regimen and levels of sCD in plasma, but this is presumably due to the low numbers of our patients receiving PIs. Previously, Fischer-Smith et al. These observations were similar when we stratified our patients using the same CD4 cutoff as Fischer—Smith and colleagues.

This might include an altered cytokine milieu in individuals at different stages of disease e. To fully elucidate the factors that modulate CD expression in HIV-1 patients, larger cohorts stratified on therapy type and comorbid disease are required.

Several studies have investigated changes in both membrane bound and soluble CD in response to acute illness. Examination of sCD levels in hospitalised patients demonstrated that sCD is an acute phase marker which increases in response to bacterial infection [5] , [8] , [32] , [35] , [36] , [37] , [74]. We did not, however, find such a correlation in our cohort of HIV-1 infected donors. Administration of endotoxin to healthy human subjects results in a rapid increase in sCD levels with concomitant loss of membrane expression on monocytes [33].

Recent investigation into the effect of chronically raised LPS serum levels on monocyte activation in HIV-1 infected people demonstrated that monocytes become resistant to the stimulating effect of LPS [75].

Monocyte tolerance to endotoxin may explain why we did not find increased sCD plasma levels and the typical changes in CD expression seen after acute exposure to endotoxin in vivo [33].

Further investigation into the effect of chronic bacterial translocation on CD expression and shedding in HIV-1 infection, and correlation with other markers of inflammation, may uncover a better understanding of chronic immune activation in HIV-1 infection.

Further studies are warranted to define these relationships before CD could be used as a prognostic indicator of HIV-1 related co-morbidities. In the early days of antiretroviral therapy, goals for treatment focused on maintaining life. Due to the success of combination antiretroviral therapy focus has shifted to maintaining the health of HIV-infected individuals.

Current antiretroviral therapy, despite effective viral suppression, does not eliminate immune activation and chronic inflammation persists, leading to an increased incidence of age-associated inflammatory diseases and a shortened lifespan. As CD is involved in immune resolution and protection against the development of atherosclerotic plaques, understanding the changes in regulation of CD in HIV-1 is important in addressing comorbid diseases caused by chronic immune activation.

Virological and immunological characteristics and antiretroviral therapy of HIV-1 infected donors at time of participation. Correlation of membrane bound CD on monocyte subsets and soluble CD in plasma stratified by clinical parameter.

We would like to acknowledge Professor Jenny Hoy and the Clinical Research Unit nursing staff at The Alfred Hospital for recruitment of patients, and all the generous blood donors used in this study. Competing Interests: The authors have declared that no competing interests exist. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Europe PMC requires Javascript to function effectively. Recent Activity. Search life-sciences literature Over 39 million articles, preprints and more Search Advanced search. Search articles by 'Emma Tippett'. Tippett E 1 ,. Cheng WJ ,. Westhorpe C ,. Cameron PU ,. Brew BJ ,. Lewin SR ,. Anthony Jaworowski Search articles by 'Anthony Jaworowski'. Jaworowski A ,. Crowe SM.

Affiliations 1 author 1. Share this article Share with email Share with twitter Share with linkedin Share with facebook. Abstract CD, a haptoglobin-hemoglobin Hp-Hb scavenger receptor, expressed by monocytes and macrophages, is important in resolution of inflammation. Here we investigated CD expression on monocyte subsets ex vivo, on cultured macrophages, and soluble in plasma, in the setting of HIV-1 infection.

Free full text. PLoS One. Published online May PMID: Cameron , 1 , 3 , 4 Bruce J. Brew , 5 Sharon R. Lewin , 1 , 2 , 3 Anthony Jaworowski , 1 , 2 , 4 and Suzanne M.

Paul U. Bruce J. Sharon R. Suzanne M. Xia Jin, Editor. Author information Article notes Copyright and License information Disclaimer. Received Nov 23; Accepted Apr Copyright Tippett et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.

This article has been cited by other articles in PMC. Associated Data Supplementary Materials Table S1: Virological and immunological characteristics and antiretroviral therapy of HIV-1 infected donors at time of participation. Table S2: Correlation of membrane bound CD on monocyte subsets and soluble CD in plasma stratified by clinical parameter. Whole blood flow cytometry phenotyping All antibodies used were purchased from BD Biosciences. Open in a separate window. Figure 1.

CD is differentially expressed on monocyte subsets at the protein and gene level. Statistics Mann-Whitney U test and Wilcoxon matched pairs test was used to test significant difference for unpaired and paired data respectively. Results CD is differentially expressed on monocyte subsets and can be induced by M-CSF stimulation Expression of CD protein on monocyte subsets in whole blood was investigated within 4 h of venepuncture by flow cytometry.

Figure 2. Figure 3. Intracellular and surface CD expression increases during maturation of monocytes to macrophages. Figure 4. Figure 5. Supporting Information Table S1 Virological and immunological characteristics and antiretroviral therapy of HIV-1 infected donors at time of participation.

DOC Click here for additional data file. Table S2 Correlation of membrane bound CD on monocyte subsets and soluble CD in plasma stratified by clinical parameter. Acknowledgments We would like to acknowledge Professor Jenny Hoy and the Clinical Research Unit nursing staff at The Alfred Hospital for recruitment of patients, and all the generous blood donors used in this study.

Footnotes Competing Interests: The authors have declared that no competing interests exist. References 1. The macrophage: the intersection between HIV infection and atherosclerosis. J Leukoc Biol. Immunocytochemical quantitation of human immunodeficiency virus in the brain: correlations with dementia.

Ann Neurol. Am J Pathol. J Neuropathol Exp Neurol. Diagnostic value of soluble CD serum levels in patients suspected of meningitis: Comparison with CRP and procalcitonin. Scand J Infect Dis. Soluble hemoglobin-haptoglobin scavenger receptor CD as a lineage-specific marker in the reactive hemophagocytic syndrome.

Eur J Haematol. The diagnostic significance of soluble CD and soluble interleukin-2 receptor alpha-chain in macrophage activation syndrome and untreated new-onset systemic juvenile idiopathic arthritis. Arthritis Rheum. Scand J Clin Lab. Identification of the haemoglobin scavenger receptor. CDexpressing monocytes constitute an endotoxin-sensitive Hb clearance compartment within the vascular system. Gating the radical hemoglobin to macrophages: the anti-inflammatory role of CD, a scavenger receptor.

Antioxid Redox Signal. J Immunol. The macrophage CD surface glycoprotein is an erythroblast adhesion receptor. The macrophage scavenger receptor CD functions as an innate immune sensor for bacteria.

Hemoglobin scavenger receptor CD mediates interleukin release and heme oxygenase-1 synthesis: antiinflammatory monocyte-macrophage responses in vitro, in resolving skin blisters in vivo, and after cardiopulmonary bypass surgery. Circ Res. Inflamm Res. The rat macrophage scavenger receptor CD expression, regulation and role in inflammatory mediator production. Hogger P, Sorg C.

Soluble CD inhibits phorbol ester-induced lymphocyte proliferation. Biochem Biophys Res Commun. Only the soluble form of the scavenger receptor CD acts inhibitory on phorbol ester-activated T-lymphocytes, whereas membrane-bound protein has no effect.

FEBS Lett. Clin Immunol. Flow cytometric assessment of monocyte activation markers and circulating endothelial cells in patients with localized or metastatic breast cancer. Cytometry B Clin Cytom. Increase in plasma and surface CD levels in patients undergoing coronary artery bypass graft surgery. Int Arch Allergy Appl Immunol. Eur J Immunol.

Regulation of scavenger receptor CD expression in human monocytes and macrophages by pro- and antiinflammatory stimuli. Up-regulation of human monocyte CD upon activation of cell-surface Toll-like receptors. Human peritoneal macrophages show functional characteristics of M-CSF-driven anti-inflammatory type 2 macrophages.

IL expression profiling in human monocytes. Cross-linking of FcgammaR triggers shedding of the hemoglobin-haptoglobin scavenger receptor CD Shedding of CD, a novel regulatory mechanism for a member of the scavenger receptor cysteine-rich family. Clin Exp Immunol. Endotoxin induces rapid metalloproteinase-mediated shedding followed by up-regulation of the monocyte hemoglobin scavenger receptor CD Pivotal advance: activation of cell surface Toll-like receptors causes shedding of the hemoglobin scavenger receptor CD Proteolytic shedding of the macrophage scavenger receptor CD in multiple sclerosis.

J Neuroimmunol. Serum levels of soluble CD correlate with the inflammatory process in coeliac disease. Aliment Pharmacol Ther. Levels of soluble CD and severity of malaria in children in Ghana.

Clin Vaccine Immunol. Human monocyte CD expression inversely correlates with soluble CD plasma levels. J Neurovirol. CD identifies perivascular macrophages in normal and viral encephalitic brains and potential precursors to perivascular macrophages in blood. Increased monocyte turnover from bone marrow correlates with severity of SIV encephalitis and CD levels in plasma.

PLoS Pathog. Phenotypic variation in myocardial macrophage populations suggests a role for macrophage activation in SIV-associated cardiac disease. The porcine 2A10 antigen is homologous to human CD and related to macrophage differentiation. Monocyte CD and CD36 expression in human whole blood and isolated mononuclear cell samples: influence of different anticoagulants. Immunobiology In press; Comparative assessment of the recognition of domain-specific CD monoclonal antibodies in human monocytes explains wide discrepancy in reported levels of cellular surface CD expression.

Nomenclature of monocytes and dendritic cells in blood. Musson RA. Surv Immunol Res.