title: Macrophage Fc receptor activity modulates mesangial cell proliferation and matrix synthesis.
abstract: 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.
authors.affiliation: Department of Medicine, Long Island Jewish Medical Center, New Hyde Park 11042.
authors.forename: J
authors.initials: J
authors.lastname: Mattana
authors.forename: P C
authors.initials: PC
authors.lastname: Singhal
mesh_terms: 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*
chemical_list: D007074:Immunoglobulin G; D011961:Receptors, Fc; D003571:Cytochalasin B; D006046:Gold; D011392:Proline