title: Distinct Effects of Integrins αXβ2 and αMβ2 on Leukocyte Subpopulations during Inflammation and Antimicrobial Responses.
abstract: Integrins αMβ2and αXβ2are homologous adhesive receptors that are expressed on many of the same leukocyte populations and bind many of the same ligands. Although αMβ2was extensively characterized and implicated in leukocyte inflammatory and immune functions, the roles of αXβ2remain largely obscure. Here, we tested the ability of mice deficient in integrin αMβ2or αXβ2to deal with opportunistic infections and the capacity of cells derived from these animals to execute inflammatory functions. The absence of αMβ2affected the recruitment of polymorphonuclear neutrophils (PMN) to bacterial and fungal pathogens as well as to model inflammatory stimuli, and αMβ2-deficient PMN displayed defective inflammatory functions. In contrast, deficiency of αXβ2abrogated 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 αXβ2resulted 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 αMβ2suppressed Mϕ egress from the peritoneal cavity, decreased the production of anti-inflammatory IL-10, and stimulated the secretion of IL-6. The absence of αXβ2, but not of αMβ2, increased survival against a septic challenge with lipopolysaccharide (LPS) by 2-fold. Together, these results suggest that αMβ2plays a primary role in PMN inflammatory functions and regulates the anti-inflammatory functions of Mϕ, whereas αXβ2is central in the regulation of inflammatory functions of recruited and tissue-resident Mϕ.
authors: Department of Molecular Cardiology, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA.
authors: Samir
authors: S
authors: Jawhara
authors: Department of Molecular Cardiology, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA.
authors: Elzbieta
authors: E
authors: Pluskota
authors: Department of Molecular Cardiology, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA.
authors: Wei
authors: W
authors: Cao
authors: Department of Molecular Cardiology, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA.
authors: Edward F
authors: EF
authors: Plow
authors: Department of Molecular Cardiology, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA solovjd@ccf.org.
authors: Dmitry A
authors: DA
authors: Soloviev
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism*; D002176:Candida albicans / Q000378:metabolism; D002177:Candidiasis / Q000378:metabolism / Q000382:microbiology; D002448:Cell Adhesion / Q000502:physiology; D004926:Escherichia coli / Q000378:metabolism; D004927:Escherichia coli Infections / Q000378:metabolism / Q000382:microbiology; D007249:Inflammation / Q000378:metabolism* / Q000382:microbiology; D016167:Integrin alphaXbeta2 / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism* / Q000382:microbiology; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism / Q000382:microbiology; D010587:Phagocytosis / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D016167:Integrin alphaXbeta2; D015850:Interleukin-6; D016177:Macrophage-1 Antigen; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: Candida albicans; Escherichia coli; animal models; cytokines; infection control; inflammation; integrins; macrophages; monocytes; neutrophils