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Originally published online as doi:10.1189/jlb.1106680 on March 27, 2007

Published online before print March 27, 2007
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(Journal of Leukocyte Biology. 2007;81:1395-1403.)
© 2007 by Society for Leukocyte Biology

CD11c/CD18: novel ligands and a role in delayed-type hypersensitivity

Chanchal Sadhu*,1, Harold J. Ting{dagger}, Brian Lipsky{ddagger}, Kelly Hensley{ddagger}, Leon F. Garcia-Martinez§, Scott I. Simon{dagger} and Donald E. Staunton||

* ICOS Corporation, Bothell, Washington, USA;
{dagger} Department of Biomedical Engineering, University of California, Davis, Davis, California, USA;
{ddagger} Amgen Inc., Seattle, Washington, USA;
§ Alder Biopharmaceutical, Bothell, Washington, USA; and
|| CisThera, Kirkland, Washington, USA

1 Correspondence: ICOS Corporation, 22021 20th Ave., S.E., Bothell, WA 98021, USA. E-mail: casdhu{at}icos.com

CD11c, a member of the leukointegrin family, is expressed prominently on tissue macrophages and dendritic cells and binds to complement fragment (iC3b), provisional matrix molecules (fibrinogen), and the Ig superfamily cell adhesion molecule, ICAM-1. CD11c has been proposed to function in phagocytosis, cell migration, and cytokine production by monocytes/macrophages as well as induction of T cell proliferation by Langerhans cells. Using assays to quantify CD11c-mediated cell adhesion, we demonstrate that CD11c recognizes ICAM-2 and VCAM-1. The CD11c-binding site on VCAM-1 appears to be different from that used by the integrin {alpha}4. CD11c and {alpha}4ß1 contributed to monocyte capture and transmigration on inflamed human aortic endothelial cells. We discovered that the anti-mouse CD11c mAb N418 blocks CD11c binding to iC3b, ICAM-1, and VCAM-1. Treatment of mice with N418 reduced SRBC-induced delayed-type hypersensitivity significantly. CD11c appeared to contribute predominantly to the sensitization phase and somewhat less to the response to SRBC challenge. This suggests a novel role for CD11c during leukocyte recruitment, antigen uptake, and the survival of APC.

Key Words: integrin • ICAM-1 • VCAM-1 • N418 • DTH




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