Heymann antigen GP330 demonstrates affinity for fibronectin, laminin, and type I collagen and mediates rat proximal tubule epithelial cell adherence to such matrices in vitro.
We have utilized monoclonal antibodies directed against glycoproteins on the surface of proximal tubule epithelial cells (PTEC) to study their interaction with matrix components. PTEC exposed to monoclonal antibodies directed against a 330-kDa cell surface glycoprotein exhibited a significant epitope-specific inhibition of attachment and proliferation on type I collagen-, fibronectin-, laminin-, and gelatin-coated tissue culture surfaces. This effect was not due to antibody toxicity since such cells did not exhibit metabolic dysfunction in suspension cultures and the inhibition could be reversed upon removal of the antibody from the cell surface. Furthermore, detergent-solubilized gp330 demonstrated specific affinity for fibronectin, laminin, and type I collagen which was not inhibited by Arg-Gly-Asp-containing peptides. A monoclonal antibody directed against the receptor epitope was capable of promoting PTEC adherence and growth when such an antibody was immobilized on cell culture dishes. Although gp330 acted as a receptor for matrix proteins in primary cultures of freshly isolated PTEC, this effect was not demonstrable in established cultures. These results suggest that freshly isolated PTEC depend on gp330 for their attachment to matrix molecules while in vitro-adapted PTEC rely on other receptors activated by culture conditions. The affinity of gp330 for matrix molecules may be of pathogenic relevance in the persistence of gp330-containing immune complexes formed in the glomerular capillary wall in experimental membranous nephropathy (Heymann nephritis).
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
D L
DL
Mendrick
D C
DC
Chung
H G
HG
Rennke
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism / Q000648:ultrastructure; D000939:Epitopes / Q000276:immunology; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D006023:Glycoproteins / Q000276:immunology; D026541:Heymann Nephritis Antigenic Complex; D016023:Integrins / Q000276:immunology / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D007797:Laminin / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
D000911:Antibodies, Monoclonal; D000939:Epitopes; D005353:Fibronectins; D006023:Glycoproteins; D026541:Heymann Nephritis Antigenic Complex; D016023:Integrins; D007797:Laminin; D008562:Membrane Glycoproteins; D003094:Collagen