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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1106680

Received for publication November 17, 2006.
Revised January 23, 2007.
Accepted for publication February 21, 2007.

Article

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

Chanchal Sadhu *@, Harold J. Ting {dagger}, Brian Lipsky {ddagger}, Kelly Hensley {ddagger}, Leon F. Garcia-Martinez {sect}, 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}Seattle, Washington, USA; {sect}Alder Biopharmaceutical, Bothell, Washington, USA; and ||CisThera, Kirkland, Washington, USA

@ To whom correspondence should be addressed. E-mail: casdhu{at}icos.com.


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Abstract

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 of 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}4{beta}1 contributed to monocyte capture and transmigration on inflamed human aortic endothelial cells. We discovered that the antimouse 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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