期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 79, 期 6, 页码 1105-1116出版社
WILEY
DOI: 10.1189/jlb.0106038
关键词
ADAM; protease; adhesion; cytokine; endothelium
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL067267, R01HL081795, P01HL018645, R01HL079273] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL018645, R01 HL081795, R01 HL079273, P01 HL018645, HL067267, R01 HL067267, HL079273] Funding Source: Medline
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.
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