title: Conditioned medium from alternatively activated macrophages induce mesangial cell apoptosis via the effect of Fas.
abstract: During inflammation in the glomerulus, the proliferation of myofiroblast-like mesangial cells is commonly associated with the pathological process. Macrophages play an important role in regulating the growth of resident mesangial cells in the glomeruli. Alternatively activated macrophage (M2 macrophage) is a subset of macrophages induced by IL-13/IL-4, which is shown to play a repair role in glomerulonephritis. Prompted by studies of development, we performed bone marrow derived macrophage and rat mesangial cell co-culture study. Conditioned medium from IL-4 primed M2 macrophages induced rat mesangial cell apoptosis. The pro-apoptotic effect of M2 macrophages was demonstrated by condensed nuclei stained with Hoechst 33258, increased apoptosis rates by flow cytometry analysis and enhanced caspase-3 activation by western blot. Fas protein was up-regulated in rat mesangial cells, and its neutralizing antibody ZB4 partly inhibited M2 macrophage-induced apoptosis. The up-regulated arginase-1 expression in M2 macrophage also contributed to this apoptotic effect. These results indicated that the process of apoptosis triggered by conditioned medium from M2 macrophages, at least is partly conducted through Fas in rat mesangial cells. Our findings provide compelling evidence that M2 macrophages control the growth of mesangial cells in renal inflammatory conditions.
authors: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors: Yuan
authors: Y
authors: Huang
authors: Fangjun
authors: F
authors: Luo
authors: Hui
authors: H
authors: Li
authors: Tao
authors: T
authors: Jiang
authors: Nong
authors: N
authors: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D019014:fas Receptor
keywords: Apoptosis; Co-culture; Macrophage; Mesangial cell