alpha subunit partners to beta1 and beta2 integrins during IL-4-induced foreign body giant cell formation.
As beta1 and beta2 integrins were previously found to mediate adhesion during IL-4-induced foreign body giant cell (FBGC) formation, we pursued the identities of the alpha integrin partners of these adhesion receptors using our in vitro system of human monocyte-derived macrophage fusion. Immunoprecipitation with beta1 and immunoblotting reveal the presence of alpha5 and alphaV, as well as alpha2 and alpha3. alphaM and alphaX immunoprecipitate with beta2 but not with beta1. Immunocytochemistry coupled with confocal microscopy indicates that alpha5 and alphaX are poorly expressed on day 0. However, following the induction of fusion by IL-4 on day 3, they are each readily detectable in fusing macrophages/FBGC on day 7. In contrast, alphaM and alphaV are present throughout the culture period, with very strong alphaM expression on day 7. We also demonstrate expression and colocalization of alpha3, alpha5, or alphaV with beta1 on fusing macrophages/FBGC at this time point as well as strong colocalization of alphaM and alphaX with beta2 in FBGC and at fusion interfaces. Therefore, IL-4-induced FBGC are characterized by the expression of alphaMbeta2, alphaXbeta2, alpha5beta1, alphaVbeta1, alpha2beta1, and alpha3beta1, which indicates potential interactions with fragments of complement C3, fibrin(ogen), fibronectin, Factor X, and vitronectin, and possibly with certain collagens, laminin, and thrombospondin at sites of biomaterial implantation.
McNally
Amy K
AK
Department of Pathology, Case Western Reserve University, Cleveland, Ohio 216-368-0279, USA. amy.mcnally@case.edu
Macewan
Sarah R
SR
Anderson
James M
JM
D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D002459:Cell Fusion; D002478:Cells, Cultured; D015743:Giant Cells, Foreign-Body / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism*; D015847:Interleukin-4 / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology
D018821:CD18 Antigens; D039001:Integrin alpha Chains; D019012:Integrin beta1; D015847:Interleukin-4