title: Force-dependent calcium signaling and its pathway of human neutrophils on P-selectin in flow.
abstract: P-selectin engagement of P-selectin glycoprotein ligand-1 (PSGL-1) causes circulating leukocytes to roll on and adhere to the vascular surface, and mediates intracellular calcium flux, a key but unclear event for subsequent arresting firmly at and migrating into the infection or injured tissue. Using a parallel plate flow chamber technique and intracellular calcium ion detector (Fluo-4 AM), the intracellular calcium flux of firmly adhered neutrophils on immobilized P-selectin in the absence of chemokines at various wall shear stresses was investigated here in real time by fluorescence microscopy. The results demonstrated that P-selectin engagement of PSGL-1 induced the intracellular calcium flux of firmly adhered neutrophils in flow, increasing P-selectin concentration enhanced cellular calcium signaling, and, force triggered, enhanced and quickened the cytoplasmic calcium bursting of neutrophils on immobilized P-selectin. This P-selectin-induced calcium signaling should come from intracellular calcium release rather than extracellular calcium influx, and be along the mechano-chemical signal pathway involving the cytoskeleton, moesin and Spleen tyrosine kinase (Syk). These results provide a novel insight into the mechano-chemical regulation mechanism for P-selectin-induced calcium signaling of neutrophils in flow.
authors.affiliation: School of Bioscience & Bioengineering, South China University of Technology, Guangzhou, 510006, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Huang
authors.affiliation: School of Bioscience & Bioengineering, South China University of Technology, Guangzhou, 510006, China.
authors.forename: Yingchen
authors.initials: Y
authors.lastname: Ling
authors.affiliation: School of Bioscience & Bioengineering, South China University of Technology, Guangzhou, 510006, China.
authors.forename: Jiangguo
authors.initials: J
authors.lastname: Lin
authors.affiliation: Hematology and Oncology Division, Guangdong General Hospital, Guangzhou, 510080, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Du
authors.affiliation: School of Bioscience & Bioengineering, South China University of Technology, Guangzhou, 510006, China. yfang@scut.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fang
authors.affiliation: School of Bioscience & Bioengineering, South China University of Technology, Guangzhou, 510006, China. wujianhua@scut.edu.cn.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wu
mesh_terms: D020013:Calcium Signaling; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D019007:P-Selectin / Q000378:metabolism*; D013314:Stress, Mechanical; D000072377:Syk Kinase / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; C000606896:SYK protein, human; D000072377:Syk Kinase
keywords: P-selectin; calcium signaling; neutrophils; shear stress