Chemokines, selectins and intracellular calcium flux

Temporal and spatial cues for leukocyte arrest

Neha Dixit, Scott I. Simon

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Leukocyte trafficking to acute sites of injury or infection requires spatial and temporal cues that fine tune precise sites of firm adhesion and guide migration to endothelial junctions where they undergo diapedesis to sites of insult. Many detailed studies on the location and gradient of chemokines such as IL-8 and other CXCR ligands reveal that their recognition shortly after selectin-mediated capture and rolling exerts acute effects on integrin activation and subsequent binding to their ligands on the endothelium, which directs firm adhesion, adhesion strengthening, and downstream migration. In this process, G-protein coupled receptor (GPCR) signaling has been found to play an integral role in activating and mobilizing intracellular stores of calcium, GTPases such as Rap-1 and Rho and cytokeletal proteins such as Talin and F-actin to facilitate cell polarity and directional pseudopod formation. A critical question remaining is how intracellular Ca2+ flux from CRAC channels such as Orai1 synergizes with cytosolic stores to mediate a rapid flux which is critical to the onset of PMN arrest and polarization. Our review will highlight a specific role for calcium as a signaling messenger in activating focal clusters of integrins bound to the cytoskeleton which allows the cell to attain a migratory phenotype. The precise interplay between chemokines, selectins, and integrins binding under the ubiquitous presence of shear stress from blood flow provides an essential cooperative signaling mechanism for effective leukocyte recruitment.

Original languageEnglish (US)
Article numberArticle 188
JournalFrontiers in Immunology
Volume3
Issue numberJUL
DOIs
StatePublished - 2012

Fingerprint

Selectins
Chemokines
Integrins
Cues
Leukocytes
Calcium
Talin
Ligands
Transendothelial and Transepithelial Migration
Cell Polarity
Pseudopodia
GTP Phosphohydrolases
G-Protein-Coupled Receptors
Cytoskeleton
Interleukin-8
Endothelium
Actins
Phenotype
Wounds and Injuries
Infection

Keywords

  • Calcium
  • Chemokine
  • Cytoskeletal proteins
  • Inflammation
  • Integrin affinity
  • LFA-1
  • Neutrophils
  • Orai1

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Chemokines, selectins and intracellular calcium flux : Temporal and spatial cues for leukocyte arrest. / Dixit, Neha; Simon, Scott I.

In: Frontiers in Immunology, Vol. 3, No. JUL, Article 188, 2012.

Research output: Contribution to journalArticle

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