Distinct Effects of Integrins αX β2 and αM β2 on Leukocyte Subpopulations during Inflammation and Antimicrobial Responses

Integrins alpha(M)beta(2) and alpha(x)beta(2) are homologous adhesive receptors that are expressed on many of the same leukocyte populations and bind many of the same ligands. Although alpha(M)beta(2) was extensively characterized and implicated in leukocyte inflammatory and immune functions, the roles of alpha(x)beta(2) remain largely obscure. Here, we tested the ability of mice deficient in integrin alpha(M)beta(2) or alpha(x)beta(2) to deal with opportunistic infections and the capacity of cells derived from these animals to execute inflammatory functions. The absence of alpha(M)beta(2) affected the recruitment of polymorphonuclear neutrophils (PMN) to bacterial and fungal pathogens as well as to model inflammatory stimuli, and alpha(M)beta(2) deficient PMN displayed defective inflammatory functions. In contrast, deficiency of alpha(x)beta(2) abrogated intraperitoneal recruitment and adhesive functions of monocytes and macrophages (M phi) and the ability of these cells to kill/phagocytose Candida albicans or Escherichia coli cells both ex vivo and in vivo. During systemic candidiasis, the absence of alpha(x)beta(2) resulted in the loss of antifungal activity by tissue M phi and inhibited the production of tumor necrosis factor alpha (TNF-alpha)/interleukin-6 (IL-6) in infected kidneys. Deficiency of alpha(M)beta suppressed M phi egress from the peritoneal cavity, decreased the production of anti-inflammatory IL10, and stimulated the secretion of IL-6. The absence of alpha(x)beta(2), but not of alpha(M)beta(2), increased survival against a septic challenge with lipopolysaccharide (LPS) by 2-fold. Together, these results suggest that alpha(M)beta(2) plays a primary role in PMN inflammatory functions and regulates the anti-inflammatory functions of M phi, whereas alpha(M)beta(2)is central in the regulation of inflammatory functions of recruited and tissue- resident M phi.