Macrophage Fc receptor activity modulates mesangial cell proliferation and matrix synthesis.
Substantial in vivo evidence exists to implicate the macrophage (M phi) in modulating mesangial expansion and glomerulosclerosis (GS) following renal injury. We studied in an in vitro system how M phi activation via Fc-receptor-mediated endocytosis, such as occurs in immune complex-mediated disease states, may influence the effect of M phi secretory products (MSP) on mesangial cell (MC) proliferation and matrix synthesis. MSP from M phi incubated with immunoglobulin G (IgG) complexes caused significantly greater (P < 0.001) enhancement of MC [3H]thymidine incorporation compared with MSP from unstimulated M phi or from M phi activated via nonspecific endocytosis (P < 0.001). MSP from M phi incubated with IgG complexes plus the inhibitor of endocytosis cytochalasin B showed an attenuated effect on MC proliferation (P < 0.02). MSP were also found to enhance MC matrix synthesis (P < 0.001). These data demonstrate that MSP can play a direct role in mesangial expansion by increasing both MC proliferation and matrix synthesis. Surface binding alone of IgG complexes may not be sufficient to activate M phi and enhance their mitogenic effect on MC as endocytosis appears to be required. These findings lend in vitro support to a potential role for the M phi in the process of mesangial expansion and GS following renal injury.
Mattana
J
J
Department of Medicine, Long Island Jewish Medical Center, New Hyde Park 11042.
Singhal
P C
PC
D002455:Cell Division; D003571:Cytochalasin B / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D005109:Extracellular Matrix / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000166:cytology* / Q000378:metabolism*; D006046:Gold; D007074:Immunoglobulin G / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000502:physiology; D010587:Phagocytosis; D011392:Proline / Q000493:pharmacokinetics; D011961:Receptors, Fc / Q000378:metabolism*
D007074:Immunoglobulin G; D011961:Receptors, Fc; D003571:Cytochalasin B; D006046:Gold; D011392:Proline