Leukocyte adhesion molecules and kidney diseases

Phagocytic leukocytes, particularly neutrophils and monocytes, are important effectors of injury in many forms of glomerulonephritis, vasculitis, tubulointerstitial nephritis and allograft rejection [1–4]. Current treatment strategies for these diseases lack immunologic specificity and are frequently toxic, reflecting our relatively naive understanding of the pathophysiology of renal inflammation. Recent advances in immunopathology research have identified leukocyte adhesion as a pivotal event in inflammation that may be amenable to therapeutic intervention. Adhesion is mediated by interaction of cell surface adhesion molecules on leukocytes with cognate ligands on resident tissue cells. The leukocyte adhesion molecules are members of larger superfamilies of cell surface receptors that play critical roles in immunosurveillance, inflammation, hemostasis, wound healing, morphogenesis, maintenance of tissue architecture, atherogenesis, and tumor metastasis. This contribution (a) reviews the classification, biochemical structures and cognate ligands of the major leukocyte adhesion molecules [5–21], (b) discusses the mechanisms by which inflammatory mediators regulate leukocyte adhesion [5–14, 22–38], (c) summarizes the distribution of leukocyte adhesion molecules in normal and diseased kidneys [12–14, 39–72], (d) highlights the dynamic interplay that occurs between leukocytes and resident tissue cells during cell-cell adhesion [73–80], and (e) reviews recent studies evaluating the efficacy of monoclonal antibodies (mAb) against leukocyte adhesion molecules in the treatment of renal inflammation [81–91]. These exciting advances may antecede the development of potent and specific new agents for the treatment of inflammatory diseases of the kidney