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The past year has witnessed continued advances along several fronts in understanding the initiation and effects of a nephritogenic immune response. New information on the major histocompatibility complex in autoimmunity suggests that major histocompatibility complex class I and class II expression is important in the initiation of the immune response. The complex pathways involved in the regulation of leukocyte recruitment in inflammation continue to unravel and the role of cytokines in these processes is being defined. The ability of antibodies directed against leukocyte adhesion molecules to attenuate inflammation in experimental glomerulonephritis opens up the possibility of new therapeutic agents for human disease. The need to reexamine the role of complement as an effector in immune renal disease is suggested by evidence of intrinsic renal complement component production. Recent information on the pathogenesis of renal scarring in crescentic glomerulonephritis suggests the importance of leukocyte-endothelial cell interaction and of delayed-type hypersensitivity in this process. The ability of the growth factors transforming growth factor-beta and platelet-derived growth factor to induce glomerulosclerosis has been documented in an innovative study using selective renal gene transfer. Finally, the potential importance of apoptosis of inflammatory cells as a mechanism limiting injury is a new focus of attention.

A postulated mechanism of immune glomerular injury is a direct interaction between antibody and glomerular epithelial cell (GEC) surface antigens. To explore this hypothesis, we examined the interaction of the noncomplement-fixing gamma 2-subclass of sheep anti-rat nephrotoxic serum (NTS), which causes immediate complement- and neutrophil-independent proteinuria in vivo, with rat GECs in culture. Reactivity of NTS with GEC surface antigens was determined by positive immunofluorescence of GEC plasma membranes and by the ability of NTS-coated tissue culture wells to provide an adhesive substrate for GECs. NTS immunoprecipitated two proteins (135 and 118 kDa) from surface-labeled GECs. Proteins of similar molecular mass were precipitated by a polyclonal rabbit antibody that identifies the beta 1-integrin chain of the mouse fibronectin receptor (anti-FnR). In addition, NTS identified similarly sized bands on Western blot analysis of cell membranes from isolated rat glomeruli. Similar reactivity was eluted from the glomeruli of proteinuric rats injected with NTS. NTS significantly inhibited GEC adhesion to laminin, types I and IV collagen, and fibronectin and prevented GEC spreading on types I and IV collagen. Anti-FnR similarly inhibited GEC adhesion. Cell viability was not affected. These results show that NTS recognizes a pair of GEC surface proteins that have the characteristics of an alpha- and beta 1-integrin and, at low concentrations, disrupt cell-matrix interactions.