Mechanisms of Immune Complex–Mediated Neutrophil Recruitment and Tissue Injury

Abstract

Deposition of antibody-antigen immune complexes (ICs)in tissues underlies the pathogenesis of a range of human autoimmune diseases from glomerulonephritis, sys-temic lupus erythematosus (SLE), arthritis, and transplanta-tion rejection to rheumatic fever. Experimental and clinical evidence suggests that autoimmunity is a risk factor for cardiovascular disease (CVD). Here, we overview the litera-ture that links autoimmune diseases and accelerated athero-sclerosis and review our understanding of IC-induced inflam-mation. In particular, we discuss the contribution of the location and composition of ICs to the cellular and molecular mechanisms of disease that develop and detail the steps leading to IC-mediated leukocyte recruitment and tissue injury. The focus is on neutrophil-dependent tissue injury. Although these cells have not found a prominent place in discussions of chronic inflammatory conditions such as au-toimmunity and atherosclerosis, recent literature discussed here indicates that neutrophils initiate IC-induced inflamma-tion that in turn launches and informs the subsequent immune response. A fuller understanding of the mechanisms involved in the initiation and perpetuation of immunoglobulin G (IgG) antibody mediated inflammation may lead to the design of innovative therapeutic strategies to prevent cardiovascular complications in patients with autoimmune diseases.