期刊
JOURNAL OF CELL SCIENCE
卷 134, 期 18, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.258046
关键词
Leukocyte adhesion; Integrin activation; Selectin; Micropipette adhesion frequency assay; Microfluidics
类别
资金
- National Institutes of Health [R01HL18671, U01CA214354, U01CA250040]
Selectins and integrins play crucial roles in recruiting leukocytes to inflamed tissues. Studies have found that E- and P-selectins have different effects on the activation of α(L)β(2), with varying responses observed at different temperatures.
Selectins and integrins are key players in the adhesion and signaling cascade that recruits leukocytes to inflamed tissues. Selectin binding induces beta(2) integrin binding to slow leukocyte rolling. Here, a micropipette was used to characterize neutrophil adhesion to E-selectin and intercellular adhesion molecule-1 (ICAM-1) at room temperature. The time-dependent adhesion frequency displayed two-stage kinetics, with an E-selectin-mediated fast increase to a low plateau followed by a slow increase to a high plateau mediated by intermediate-affinity binding of integrin alpha(L)beta(2) to ICAM-1. The alpha(L)beta(2) activation required more than 5 s contact to E-selectin and spleen tyrosine kinase (Syk) activity. A multi-zone channel was used to analyze izA activation by P-selectin in separate zones of receptors or antibodies, finding an inverse relationship between the rolling velocity on ICAM-1 and P-selectin dose, and a P-selectin dose-dependent change from bent to extended conformations with a closed headpiece that was faster at 37 degrees C than at room temperature. Activation of alpha(L)beta(2) exhibited different levels of cooperativity and persistent times depending on the strength and duration of selectin stimulation. These results define the precise timing and kinetics of intermediate activation of alpha(L)beta(2) by E- and P-selectins.
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