|
|||||||||
|
|
|
|
|
|
|
|
|
|
|
Blood, 15 June 2006, Vol. 107, No. 12, pp. 4938-4945. Prepublished online as a Blood First Edition Paper on March 2, 2006; DOI 10.1182/blood-2005-09-3803.
PHAGOCYTES E-selectin permits communication between PAF receptors and TRPC channels in human neutrophilsFrom the Medical Research Council (MRC) Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, United Kingdom.
The selectin family of molecules (L-, P-, and E-selectin) mediates adhesive interactions between leukocytes and endothelial cells required for recruitment of leukocytes to inflammatory sites. Soluble E-selectin levels are elevated in inflammatory diseases and act to promote neutrophil
This article has been cited by other articles:
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
 |
 |
|||||||
 |
 |
 |
 |
 |
 |
 |
 |
||
| Copyright © 2006 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
2-integrin–mediated adhesion by prolonging Ca2+ mobilization. Although soluble E-selectin alone was unable to initiate Ca2+ signaling, it allowed a novel "permissive" store-operative calcium entry (SOCE) following the initial platelet-activating factor (PAF)–induced release of Ca2+ from inositol 1,4,5-trisphosphate (IP3)–sensitive stores. This induction of permissive SOCE in response to soluble E-selectin and PAF was shown to act through a G protein-coupled receptor (GPCR) coupled to pertussis toxin-insensitive Gq/11. Furthermore, we demonstrated that permissive SOCE was mediated by canonical transient receptor potential channel (TRPC) due to its sensitivity to specific inhibition by MRS1845 and Gd3+ and that TRPC6 was the principal TRPC family member expressed by human neutrophils. In terms of mechanism, we demonstrated that soluble E-selectin activated Src family tyrosine kinases, an effect that was upstream of phosphatidylinositol 3'-kinase in a signaling pathway that regulates permissive SOCE following exposure of neutrophils to PAF. In summary, this report provides the first evidence for communication between an inflammatory mediator and adhesion receptors at a molecular level, through selectin receptor ligation allowing permissive SOCE to occur following PAF stimulation of human neutrophils. 
