CD11c/CD18: novel ligands and a role in delayed-type hypersensitivity.
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 alpha4. CD11c and alpha4beta1 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.
Sadhu
Chanchal
C
ICOS Corporation, 22021 20th Ave., S.E., Bothell, WA 98021, USA. casdhu@icos.com
Ting
Harold J
HJ
Lipsky
Brian
B
Hensley
Kelly
K
Garcia-Martinez
Leon F
LF
Simon
Scott I
SI
Staunton
Donald E
DE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D001011:Aorta / Q000166:cytology; D001665:Binding Sites; D039521:CD11c Antigen / Q000276:immunology* / Q000378:metabolism; D018821:CD18 Antigens / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D003179:Complement C3b / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology / Q000502:physiology; D004912:Erythrocytes / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D039441:Integrin alpha4 / Q000378:metabolism; D008024:Ligands; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000502:physiology; D011485:Protein Binding; D012756:Sheep; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D039521:CD11c Antigen; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D008024:Ligands; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4; D003179:Complement C3b