The Role of Integrins αMβ2 (Mac-1, CD11b/CD18) and αDβ2 (CD11d/CD18) in Macrophage Fusion

Am J Pathol. 2016 Aug;186(8):2105-2116. doi: 10.1016/j.ajpath.2016.04.001. Epub 2016 Jun 14.

Abstract

The subfamily of β2 integrins is implicated in macrophage fusion, a hallmark of chronic inflammation. Among β2 family members, integrin Mac-1 (αMβ2, CD11b/CD18) is abundantly expressed on monocyte/macrophages and mediates critical adhesive reactions of these cells. However, the role of Mac-1 in macrophage fusion leading to the formation of multinucleated giant cells remains unclear. Moreover, the role of integrin αDβ2 (CD11d/CD18), a receptor with recognition specificity overlapping that of Mac-1, is unknown. We found that multinucleated giant cells are formed in the inflamed mouse peritoneum during the resolution phase of inflammation, and their numbers were approximately twofold higher in wild-type mice than in Mac-1(-/-) mice. Analyses of isolated inflammatory peritoneal macrophages showed that IL-4-induced fusion of Mac-1-deficient cells was strongly reduced compared with wild-type counterparts. The examination of adhesive reactions known to be required for fusion showed that spreading, but not adhesion and migration, was reduced in Mac-1-deficient macrophages. Fusion of αDβ2-deficient macrophages was also significantly decreased, albeit to a smaller degree. Deficiency of intercellular adhesion molecule 1, a counter-receptor for Mac-1 and αDβ2, did not alter the fusion rate. The results indicate that both Mac-1 and αDβ2 support macrophage fusion with Mac-1 playing a dominant role and suggest that Mac-1 may mediate cell-cell interactions with a previously unrecognized counter-receptor(s).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD11 Antigens / metabolism*
  • Cell Fusion
  • Disease Models, Animal
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Giant Cells / cytology
  • Giant Cells / metabolism
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Integrin alpha Chains / metabolism*
  • Macrophage-1 Antigen / metabolism*
  • Macrophages / cytology*
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peritonitis

Substances

  • CD11 Antigens
  • Integrin alpha Chains
  • Macrophage-1 Antigen
  • integrin alphaD, mouse