Differential Induction of Apoptosis by Fas–Fas Ligand Interactions in Human Monocytes and Macrophages

Kiener, Peter A.; Davis, Patricia M.; Starling, Gary C.; Mehlin, Christopher; Klebanoff, Seymour J.; Ledbetter, Jeffrey A.; Liles, W. Conrad

doi:10.1084/jem.185.8.1511

Cited by 236 publications

(210 citation statements)

References 29 publications

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“…The Fas/FasL system is believed to play an important role in normal monocyte physiology (16). Monocytes are able to undergo apoptosis via an autocrine or paracrine mechanism that is dependent upon the expression of both Fas and FasL (40). This has been confirmed by in vitro studies which have shown that anti-Fas or anti-FasL neutralizing Abs can block monocyte spontaneous apoptosis during differentiation (40).…”

Section: Discussionsupporting

confidence: 52%

Interaction of the Estrogen Receptors with the Fas Ligand Promoter in Human Monocytes

Mor

Sapi

Abrahams

et al. 2003

The Journal of Immunology

167

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The predominance of autoimmune diseases among women suggests that estrogen may modulate immune function. Monocytes and macrophages are important in initiating, maintaining, and resolving inflammatory responses through cell-signaling molecules, which control immune cell survival. One important mechanism of cell survival is mediated by the Fas/Fas ligand (FasL) system. In this study, the link between estrogen, monocytes/macrophages, and the Fas/FasL system was investigated. Estrogen treatment increased FasL expression in monocytes through the binding of the estrogen receptors (ER) to the estrogen recognizing elements and AP-1 motifs present at the FasL promoter. Furthermore, estrogen induced apoptosis in monocytes expressing ERβ, but not in monocyte-differentiated macrophages expressing ERα. The expression of either ERα or ERβ and their response to estrogen in monocytes was found to be dependent on the their stage of cell differentiation. Previously, we have shown that estrogen replacement therapy in postmenopausal women decreased the number of circulating monocytes. In this study, we have characterized the molecular mechanism by which estrogen regulates monocytes homeostasis. These findings indicate that estrogen may regulate immune cell survival through the Fas/FasL system. There is biological relevance to these findings in view of studies showing that accumulation of activated monocytes is involved in the pathogenesis of conditions such as vasculititis, arteriosclerosis, and rheumatoid arthritis.

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Section: Discussionsupporting

confidence: 52%

Interaction of the Estrogen Receptors with the Fas Ligand Promoter in Human Monocytes

Mor

Sapi

Abrahams

et al. 2003

The Journal of Immunology

167

View full text Add to dashboard Cite

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“…Peripheral blood monocytes were then isolated from the MNCs by countercurrent centrifugal elutriation (Beckman Coulter, Palo Alto, CA) (13,14). Monocytes were differentiated to macrophages in RPMI 1640 containing 20% heat-inactivated fetal bovine serum (FBS) and 1 g/ml polymyxin B sulfate (Sigma) (15,16). All experiments using human cells were approved by the Institutional Review Boards of Northwestern University and Saint Louis University.…”

Section: Methodsmentioning

confidence: 99%

Rheumatoid arthritis synovial fluid macrophages express decreased tumor necrosis factor–related apoptosis‐inducing ligand R2 and increased decoy receptor tumor necrosis factor–related apoptosis‐inducing ligand R3

Perlman¹,

Nguyen²,

Liu³

et al. 2003

Arthritis & Rheumatism

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Objective. To characterize the expression pattern of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its cognate receptors (TRAIL R1, R2, R3, and R4) on rheumatoid arthritis (RA) synovial fluid (SF) lymphocytes and monocyte/macrophages and on cultured RA synovial fibroblasts.Methods. The expression of TRAIL and TRAIL receptors on RA SF lymphocytes and monocyte/macrophages, normal macrophages, and RA synovial fibroblasts was examined by flow cytometry with previously characterized monoclonal antibodies. The ability of adenoviral-mediated delivery of TRAIL to induce macrophage or RA synovial fibroblast apoptosis was examined by flow cytometry.Results. By flow cytometry, neither TRAIL nor its cognate receptors was detectable on RA SF lymphocytes or RA synovial fibroblasts. In contrast, RA SF macrophages expressed TRAIL R3, a decoy receptor (P < 0.01 versus isotype control), but not TRAIL, or TRAIL R1, R2, or R4. Normal peripheral blood-derived monocytedifferentiated macrophages expressed TRAIL R2 (P < 0.01), but not TRAIL or the other TRAIL receptors. Adenoviral-mediated delivery of TRAIL had no effect on the survival of normal macrophages or RA synovial fibroblasts but readily induced apoptosis in the prostate cancer cell line (PC-3) that expressed TRAIL R1 and R2.Conclusion. TRAIL R1 and R2, which are required for signal transmission by TRAIL, were not detected on RA SF lymphocytes, macrophages, or synovial fibroblasts. These observations do not support a potential therapeutic role for TRAIL in RA.

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“…15,16 Conversely, activation of monocytes by LPS or TNF-␣ promotes pro-inflammatory-induced monocyte survival. 16 The fact that we observed an increase in the frequency and absolute numbers of circulating monocytes in patients with PBC compared with sex-matched controls of similar age suggests that monocytes were activated in vivo as a result of chronic inflammation endured by the patients. As such, freshly isolated monocytes from patients, as opposed to normal controls, are more resistant to self-induced cellular death because of their activation status.…”

Section: Discussionmentioning

confidence: 99%

Altered Monocyte Responses to Defined TLR Ligands in Patients With Primary Biliary Cirrhosis *

et al. 2005

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The role of the adaptive immune response, with regard to the development of autoantibodies, has been extensively studied in primary biliary cirrhosis (PBC). However, the importance of innate immunity has been noted only recently. Based on the proposed role of microorganisms in the pathogenesis of the disease, we hypothesize that patients with PBC possess a hyper-responsive innate immune system to pathogen-associated stimuli that may facilitate the loss of tolerance. To address this issue, we isolated peripheral blood monocytes from 33 patients with PBC and 26 age-matched healthy controls and stimulated such cells in vitro with defined ligands for toll-like receptor (

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Differential Induction of Apoptosis by Fas–Fas Ligand Interactions in Human Monocytes and Macrophages

Cited by 236 publications

References 29 publications

Interaction of the Estrogen Receptors with the Fas Ligand Promoter in Human Monocytes

Interaction of the Estrogen Receptors with the Fas Ligand Promoter in Human Monocytes

Rheumatoid arthritis synovial fluid macrophages express decreased tumor necrosis factor–related apoptosis‐inducing ligand R2 and increased decoy receptor tumor necrosis factor–related apoptosis‐inducing ligand R3

Altered Monocyte Responses to Defined TLR Ligands in Patients With Primary Biliary Cirrhosis *

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