A systemic lupus erythematosus-associated R77H substitution in the CD11b chain of the Mac-1 integrin compromises leukocyte adhesion and phagocytosis.

ABSTRACT: The Mac-1 integrin is expressed mainly on myeloid cells and binds several ligands, including members of the ICAM family and the complement factor iC3b. It is involved in essential immunological processes, such as leukocyte extravasation and phagocytosis. In addition, Mac-1 has been described to negatively regulate immune cell signaling. Recently, a single nucleotide polymorphism conferring an amino acid change in the Mac-1 integrin extracellular domain, R77H, was shown to be associated with systemic lupus erythematosus. Here, we demonstrate that the R77H-substituted Mac-1 can be expressed on the cell surface in transfected cells and can undergo conformational changes in response to integrin activation. The affinity of the integrin for ICAMs is only partially reduced, but cell adhesion to I

SUBMITTER: MacPherson M 

PROVIDER: S-EPMC3089572 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature