Format

Send to

Choose Destination
Blood. 2001 May 15;97(10):3251-8.

Phosphoinositide 3-kinase modulation of beta(3)-integrin represents an endogenous "braking" mechanism during neutrophil transmatrix migration.

Author information

1
Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Abstract

During episodes of inflammation, neutrophils (polymorphonuclear leukocytes [PMNs]) encounter subendothelial matrix substrates that may require additional signaling pathways as directives for movement through the extracellular space. Using an in vitro endothelial and epithelial model, inhibitors of phosphoinositide 3-kinase (PI3K) were observed to promote chemoattractant-stimulated migration by as much as 8 +/- 0.3-fold. Subsequent studies indicated that PMNs respond in a similar manner to RGD-containing matrix substrates and that PMN-matrix interactions are potently inhibited by antibodies directed against beta(3)- but not beta(1)-integrin antibodies, and that PI3K inhibitors block beta(3)-integrin dependence. Biochemical analysis of intracellular beta(3)-integrin uncoupling by PI3K inhibitors revealed diminished beta(3)-integrin tyrosine phosphorylation and decreased association with p72(syk). Similarly, the p72(syk) inhibitor piceatannol promoted PMN transmatrix migration, whereas HIV-tat peptide-facilitated loading of peptides corresponding to the beta(3)-integrin cytoplasmic tail identified the functional tyrosine residues for this activity. These data indicate that PI3K-regulated beta(3)-integrin represents a natural "braking" mechanism for PMNs during transit through the extracellular matrix.

PMID:
11342456
DOI:
10.1182/blood.v97.10.3251
[Indexed for MEDLINE]
Free full text

Publication types, MeSH terms, Substances, Grant support

Supplemental Content

Full text links

Icon for HighWire Icon for University of Colorado, Strauss Health Sciences Library
Loading ...
Support Center