Spatiotemporal characteristics of P-selectin-induced β2 integrin activation of human neutrophils under flow

Autor: Xiaoxi Sun, Bing Huang, Yuping Pan, Jinhua Fang, Hefeng Wang, Yanru Ji, Yingchen Ling, Pei Guo, Jiangguo Lin, Quhuan Li, Ying Fang, Jianhua Wu
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Frontiers in Immunology, Vol 13 (2022)
Druh dokumentu: article
ISSN: 1664-3224
DOI: 10.3389/fimmu.2022.1023865
Popis: Activation of integrins is crucial for recruitment of flowing leukocytes to inflammatory or injured vascular sites, but their spatiotemporal characteristics are incompletely understood. We discovered that β2-integrin activation over the entire surface of neutrophils on immobilized P-selectin occurred via mitogen-activated protein kinase (MAPK) or non-MAPK signaling with a minute-level timescale in a force-dependent manner. In flow, MAPK signaling required intracellular Ca2+ release to activate integrin within 2 min. Integrin activation via non-MAPK signaling occurred first locally in the vicinity of ligated P-selectin glycoprotein ligand-1 (PSGL-1) within sub-seconds, and then over the entire cell surface within 1 min in an extracellular Ca2+ influx-dependent manner. The transition from a local (but rapid) to global (but slow) activation mode was triggered by ligating the freshly activated integrin. Lipid rafts, moesin, actin, and talin were involved in non-MAPK signaling. Fluid loads had a slight effect on local integrin activation with a second-level timescale, but served as enhancers of global integrin activation.
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