Integrin CD11c contributes to monocyte adhesion with CD11b in a differential manner and requires Src family kinase activity

Integrin-mediated adhesion of human monocytes to fibrinogen regulated by CD11b/CD18 and the closely related integrin CD11c/CD18, play a key role in inflammation. Peripheral blood monocytes isolated from human donors despite expressing CD11c primarily utilized CD11b to mediate adhesion to fibrinogen upon stimulation with granulocyte macrophage-colony stimulating factor (GM-CSF) and fMLP. Blocking with anti-CD11b resulted in 90% (p < 0.001, n =3) inhibition of monocyte adhesion. Monocytes cultured in human serum showed a shift in the participation of integrins, adhesion to fibrinogen involving both CD11b and CD11c. The participation of CD11c in cultured monocytes corresponded to a 3.4-fold increase in expression in CD11c. Blocking cultured monocytes with anti-CD11b or anti-CD11c alone showed no significant effect on adhesion. Treatment with both anti-CD11b and anti-CD11c resulted in inhibition of adhesion by 85% (p < 0.001, n = 3). Abrogation in adhesion upon treatment with PP1 or PP2 showed that Src family kinase activity was required for CD11b and CD11c mediated adhesion of cultured monocytes to fibrinogen upon stimulation with GM-CSF and fMLP. The clustering of CD11c on cultured monocytes upon adhesion to fibrinogen was diminished on inhibition with PP2 indicating a role for Src family kinase activity in regulating CD11c avidity. CD11b was critical to cytoskeletal events leading to increased spreading and formation of actin foci in cultured monocytes following adhesion to fibrinogen. Blocking cultured monocytes with anti-CD11b or anti-CD11c alone showed that the increase in spread area was diminished by 67 +/- 3% and 36 +/- 9%, respectively. The differential involvement of CD11c and CD11b in adhesion and subsequent cytoskeletal changes in monocytes exposed to different conditions indicates the importance of each integrin in distinct responses during inflammation. (C) 2008 Elsevier Ltd. All rights reserved.