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Role of α4β1 Integrins in Chemokine‐Induced Monocyte Arrest under Conditions of Shear Stress
Author(s) -
HYDUK SHARON J.,
CYBULSKY MYRON I.
Publication year - 2009
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1080/10739680802425195
Subject(s) - microbiology and biotechnology , monocyte , integrin , chemokine , cell adhesion molecule , chemistry , cell adhesion , receptor , adhesion , biology , immunology , biochemistry , organic chemistry
ABSTRACT Monocyte recruitment or emigration to tissues is an essential component of host defense in both acute and chronic inflammatory responses. Sequential molecular interactions mediate a cascade of tethering, rolling, arrest, stable adhesion, and intravascular crawling that culminates in monocyte diapedesis across the vascular endothelium and migration through the basement membrane of postcapillary venules. Integrins are complex adhesion and signaling molecules. Dynamic alterations in their conformation and distribution on the monocyte cell surface are required for many steps of monocyte emigration. Intracellular signaling initiated by chemokine receptors induces conformational changes in integrins that upregulate their affinity for ligands, and this is essential for monocyte arrest. This review focuses on the activation of monocyte α4β1 integrins by endothelial chemokines, which is required for the arrest of monocytes rolling on vascular cell adhesion molecule 1 under shear flow. Using soluble ligand‐binding assays and adhesion assays in parallel‐plate flow chambers, critical signaling mediators in chemokine‐induced α4β1 integrin affinity upregulation and monocyte arrest have been identified, including phospholipase C, calcium, and calmodulin.