Immune deposits formed in situ by a monoclonal antibody recognizing a new intrinsic rat mesangial matrix antigen.
We describe a unique mesangial matrix component of the rat glomerulus identified by a murine monoclonal antibody. The antigen is present exclusively in the glomerular mesangium and cannot be detected in other rat tissues by indirect immunofluorescence techniques or following pretreatment of tissue sections with acid urea or other nonionic detergents. Specific immunoprecipitation of the solubilized antigen yields a single peptide with an apparent m.w. of 81,000 when analyzed by discontinuous SDS-PAGE. This mesangial matrix component is collagenase resistant and trypsin sensitive. Perfusion of an isolated kidney preparation with this antibody results in direct binding of the mouse immunoglobulin to its mesangial antigen. Passive administration of the monoclonal antibody to Lewis rats results in characteristic electron dense deposits within the mesangial matrix that can be visualized ultrastructurally as early as 3 days. The immune deposits form without the activation of rat complement and persist for longer periods than those that develop after the planting of aggregated proteins or preformed immune complexes. Experimental animals that received either a monoclonal antibody specific for laminin or a non-kidney binding preparation did not develop such immune deposits at any time during the course of the autologous phase of the immune process. The results obtained in this study indicate that electron dense immune deposits can develop in the mesangium with the participation of a unique intrinsic matrix component and specific circulating monoclonal antibodies by an in situ mechanism of immune complex formation.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000032:analysis*; D000941:Antigens / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000276:immunology* / Q000648:ultrastructure; D007797:Laminin / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011917:Rats, Inbred Lew
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000941:Antigens; D007797:Laminin; C049900:mesangial matrix antigen