Emerging roles for ectodomain shedding in the regulation of inflammatory responses

Journal of Leukocyte Biology

Kyle J. Garton¹  Elaine W. Raines¹  Peter J. Gough¹ 

[1] Department of Pathology, University of Washington, Harborview Medical Center, SeattleDepartment of Pathology, University of Washington, Harborview Medical Center, SeattleDepartment of Pathology, University of Washington, Harborview Medical Center, Seattle

关键词: ADAM;    protease;    adhesion;    cytokine;    endothelium;   

DOI  :  10.1189/jlb.0106038

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

The multistep model of leukocyte recruitment to sites of inflammation has helped elucidate specific molecular cues for each of the individual steps. However, it is less clear how cells transition between the different steps and how the complex interactions are coordinately regulated. Once a leukocyte sticks to the endothelium, it only takes a few minutes to reach the subendothelial basement membrane, so the transitions and regulatory mechanisms must be rapid. We put forward the hypothesis that proteolytic shedding of cell surface proteins provides a mechanism to aid in the rapid transition of cells and coordinate the complex, multistep process of leukocyte recruitment in response to inflammatory stimuli. Support for this hypothesis is provided from analyses of disease states and from studies with protease inhibitors and genetically engineered mutations that prevent “ectodomain shedding” of cell surface proteins and consequently perturb the inflammatory response.

【 授权许可】

Unknown