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CD11c/CD18: novel ligands and a role in delayed-type hypersensitivity
Chanchal Sadhu1, Harold J Ting, Brian Lipsky
1ICOS Corporation, 22021 20th Ave., S.E., Bothell, WA 98021, USA. casdhu@icos.com
Journal of Leukocyte Biology
|March 29, 2007
Summary
CD11c, a key molecule on immune cells, mediates cell adhesion and migration. Blocking CD11c function significantly reduces immune responses, suggesting its crucial role in leukocyte recruitment and antigen presentation.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- CD11c (leukointegrin family) is expressed on macrophages and dendritic cells.
- It binds to iC3b, fibrinogen, and ICAM-1.
- Proposed roles include phagocytosis, migration, cytokine production, and T cell proliferation.
Purpose of the Study:
- To investigate CD11c's binding interactions with ICAM-2 and VCAM-1.
- To assess CD11c's contribution to monocyte adhesion and transmigration.
- To evaluate the in vivo effect of anti-CD11c antibody on immune responses.
Main Methods:
- Cell adhesion assays to quantify CD11c-mediated binding.
- Monocyte transmigration assays on inflamed endothelial cells.
- In vivo studies using anti-mouse CD11c mAb N418 in a delayed-type hypersensitivity model.
Main Results:
- CD11c was found to recognize ICAM-2 and VCAM-1.
- CD11c and alpha4beta1 synergistically promoted monocyte capture and transmigration.
- Anti-CD11c antibody (N418) blocked CD11c binding to iC3b, ICAM-1, and VCAM-1.
- N418 treatment significantly reduced SRBC-induced delayed-type hypersensitivity.
Conclusions:
- CD11c plays a significant role in leukocyte recruitment and antigen uptake.
- CD11c is crucial for the sensitization phase of immune responses.
- This study suggests novel functions for CD11c in antigen-presenting cell (APC) survival and immune cell trafficking.
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