- 作者: Jeremy J. Rose; John F. Foley; Ling Yi; Gina Herren; Sundararajan Venkatesan
- 作者服務機構: Laboratory of Molecular Immunology, National Instituteof Allergy and Infectious Diseases, National Institutes of Health, MD, USA
- 中文摘要: --
- 英文摘要: Plasma membrane cholesterol is critical forneutrophil chemotaxis, although how cholesterol affectschemotactic signaling pathway has not been clearlydelineated. Here we demonstrate that cholesterol wasabsolutely required for polarized redistribution of keychemotactic mediators in human neutrophils in response toall chemoattractants tested (fMet-Leu-Phe, and the chemokinesCXCL1, CXCL8 and CXCL12). In particular,PI3K and phosphatidylinositol-3,4,5 triphosphate (PIP3)failed to accumulate at the front and phosphatase and tensinhomolog (PTEN) at the back of chemoattractant-stimulatedneutrophils after cholesterol depletion. Cholesterol depletiondid not affect early chemoattractant signaling eventssuch as G-protein activation, intracellular calcium flux orG-protein-independent endocytosis-linked signaling,including the activation of mitogen-activated proteinkinase (MAPK), Hck and Fgr transduced by b-arrestin.During cell polarization, F-actin assemblies redistributedthe cholesterol-rich microdomains and cytoskeletonanchoredproteins, including CD16 and CD44 from theleading edge. These data suggest that spatial polarization ofchemotactic mediators is orchestrated by protein:proteininteractions that organize cholesterol-rich domains of theplasma membrane.
- 中文關鍵字: --
- 英文關鍵字: Neutrophils; Chemotaxis; Cholesterol; Lipid rafts; Chemoattractants; G-proteins; Endocytosis; Arrestin; Degranulation; Protein kinases; F-actin