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A Microphysiological System to Study Leukocyte-Endothelial Cell Interaction during Inflammation
Published on: December 9, 2021
P-selectin primes leukocyte integrin activation during inflammation.
Hai-Bo Wang1, Jin-Tao Wang, Lei Zhang
1Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Graduate School of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Nature Immunology
|July 17, 2007
Summary
P-selectin glycoprotein ligand 1 initiates a signaling pathway that activates leukocyte integrins, crucial for cell adhesion and infiltration. This discovery clarifies how selectins control leukocyte behavior in vivo.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Selectins mediate initial leukocyte rolling and prime cells for adhesion.
- The in vivo significance and signaling mechanisms of selectin-mediated integrin activation remain unclear.
Purpose of the Study:
- To elucidate the in vivo role and signaling pathway of P-selectin glycoprotein ligand 1 (PSGL-1) in leukocyte integrin activation.
Main Methods:
- Utilized P-selectin-deficient mice and soluble P-selectin for rescue experiments.
- Investigated protein interactions and phosphorylation events involving PSGL-1, Nef-associated factor 1, Src kinases, and phosphoinositide-3-OH kinase (PI3K).
- Assessed leukocyte adhesion and infiltration in vivo following pathway inhibition.
Main Results:
- P-selectin-deficient mice showed reduced leukocyte adhesion, rescued by soluble P-selectin.
- PSGL-1's cytoplasmic domain constitutively complexes with Nef-associated factor 1.
- P-selectin binding triggers Src kinase phosphorylation of Nef-associated factor 1, recruiting PI3K (p85-p110delta) and activating leukocyte integrins.
- Inhibiting this pathway decreased leukocyte adhesion and peritoneal infiltration.
Conclusions:
- Identified a novel signaling pathway initiated by PSGL-1 that mediates selectin-induced leukocyte integrin activation.
- Demonstrated the functional importance of this pathway in regulating leukocyte adhesion and inflammatory cell infiltration in vivo.
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Overview