Leukocyte migration in immune complex glomerulonephritis: role of adhesion receptors.

Abstract

The application of our evolving knowledge of adhesion receptors to experimental models of immune complex glomerulonephritis has led to substantial advances in our understanding of how leukocytes emigrate from the vasculature into glomeruli and produce glomerular dysfunction. With respect to neutrophil (PMN) migration and activation in the context of nephritis, the adhesion molecules alpha M beta 2, alpha IIb beta 3, and intercellular adhesion molecule-1 (ICAM-1) seem to be most essential, with more modest (and less well defined) contributions by P-selectin, alpha 4 beta 1, and vascular cell adhesion molecule-1 (VCAM-1). The influx of PMNs is driven largely by complement and alpha chemokines. In contrast to PMNs, monocyte/macrophage migration and activation during nephritis appear to be largely mediated by the adhesion molecules alpha L beta 2, alpha 4 beta 1, ICAM-1, VCAM-1, and potentially P-selectin. Monocyte/macrophage migration also differs from that of PMNs in that it is complement-independent and involves beta chemokines. Further refinement of our understanding of the role of adhesion receptors in immune glomerulonephritis may eventually lead to clinically applicable strategies to ameliorate glomerular inflammation and resulting glomerulosclerosis.