Expression and function of semaphorin 3A and its receptors in human monocyte-derived macrophages.
Semaphorins are a large family of secreted and membrane-bound proteins. Recently, several roles of semaphorins in the immune system have emerged. Several semaphorins and their receptors are expressed in a variety of lymphoid and myeloid cells and affect immune cell functions, including cell proliferation, differentiation, chemotaxis, and cytokine production. However, the roles of class 3 semaphorins in human myeloid cells are not well known. Here we examined the regulation of expression of class 3 semaphorins and their receptors by inflammatory stimuli and their function in human macrophages. We show that the expression of Sema3A receptors (neuropilin-1 (NRP-1), NRP-2, plexin A1, plexin A2, and plexin A3) significantly increased during M-CSF-mediated differentiation of monocytes into macrophages under conditions that promote an M2 alternatively activated macrophage phenotype. Consistent with increased NRP-1 expression, cell surface binding of Sema3A increased during M2 differentiation. Interferon (IFN)-gamma and lipopolysaccharide, which promote classical M1 macrophage activation affected expression of NRP-1, NRP-2 and plexin A1. IFN-gamma decreased NRP-1 expression and LPS suppressed NRP-2 and plexin A1 expression. Furthermore we show that Sema3A induced apoptosis in monocyte-derived macrophages and cooperated with anti-Fas CH11 antibody to augment apoptosis. Our results suggest that Sema3A plays a role in induction of apoptosis in monocyte-derived macrophages that are resistant to Fas-induced apoptosis, and that its function can be modulated in inflammatory conditions.
Ji
Jong-Dae
JD
Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, New York, USA.
Park-Min
Kyung-Hyun
KH
Ivashkiv
Lionel B
LB
D017209:Apoptosis; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D039942:Neuropilin-1 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D039943:Neuropilin-2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D010587:Phagocytosis; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D040121:Semaphorin-3A / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; C492116:PLXNA1 protein, human; C515995:PLXNA2 protein, human; C097871:PLXNA3 protein, human; D011956:Receptors, Cell Surface; D040121:Semaphorin-3A; D039942:Neuropilin-1; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma