Distinct Effects of Integrins αXβ2 and αMβ2 on Leukocyte Subpopulations during Inflammation and Antimicrobial Responses.

Integrins αM β2 and αX β2 are homologous adhesive receptors that are expressed on many of the same leukocyte populations and bind many of the same ligands. Although αM β2 was extensively characterized and implicated in leukocyte inflammatory and immune functions, the roles of αX β2 remain largely obscure. Here, we tested the ability of mice deficient in integrin αM β2 or αX β2 to deal with opportunistic infections and the capacity of cells derived from these animals to execute inflammatory functions. The absence of αM β2 affected the recruitment of polymorphonuclear neutrophils (PMN) to bacterial and fungal pathogens as well as to model inflammatory stimuli, and αM β2 -deficient PMN displayed defective inflammatory functions. In contrast, deficiency of αX β2 abrogated intraperitoneal recruitment and adhesive functions of monocytes and macrophages (Mϕ) 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 αX β2 resulted in the loss of antifungal activity by tissue Mϕ and inhibited the production of tumor necrosis factor alpha (TNF-α)/interleukin-6 (IL-6) in infected kidneys. Deficiency of αM β2 suppressed Mϕ egress from the peritoneal cavity, decreased the production of anti-inflammatory IL-10, and stimulated the secretion of IL-6. The absence of αX β2 , but not of αM β2 , increased survival against a septic challenge with lipopolysaccharide (LPS) by 2-fold. Together, these results suggest that αM β2 plays a primary role in PMN inflammatory functions and regulates the anti-inflammatory functions of Mϕ, whereas αX β2 is central in the regulation of inflammatory functions of recruited and tissue-resident Mϕ.