IngentaConnect beta2 Integrin modulates platelet caspase activation and life spa...

Authors: Piguet P.F.¹; Vesin C.¹; Rochat A.¹

Source: European Journal of Cell Biology, Volume 80, Number 2, February 2001 , pp. 171-177(7)

Abstract:

We explored the role of CD18 ( beta 2 integrin) in platelet physiology, using mice genetically deficient in CD18 (CD18 -/-), or its main ligand CD54 (ICAM-1, CD54 -/-). CD18 and CD11a were evident in platelets from +/+, but not from CD18 -/- mice, as seen by immunofluorescence or Western blots. CD18 mRNA was also detectable by RT-PCR in platelets from +/+, but not from CD18 -/- mice. The life span of platelets was significantly shorter in CD18 -/- than in +/+ or CD54 -/- mice, as seen by in vivo biotinylation. When a local inflammation was elicited by the intra-tracheal injection of TNF, labeled platelets from +/+, but not from CD18 -/- donors, did localize in the lung. The content of Bcl-3 was about 20-fold higher in platelet from CD18 -/-, than in those from +/+ or CD54 -/- donors, as seen on Western blots or by immunofluorescence and flow cytometry, while the amount of pro-caspase-3 was decreased. An activation of caspases in platelets from CD18 -/- was also evidenced by protease assays. Accordingly, gelsolin, a protein cleaved by caspase-3, showed a low-molecular-weight band in platelets from CD18 -/- but not from +/+ donors. These results demonstrate that the beta 2 integrin, present in mouse platelets, modulates caspase activation and consequently platelet life span and response to TNF.

Keywords: Platelet; kinetics; CD18; CD54; Bcl-3; caspase-3

Language: English

Document Type: Original article

DOI: 10.1078/0171-9335-00147

Affiliations: 1: Department of Pathology, University of Geneva, Geneva/Switzerland

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2 Integrin modulates platelet caspase activation and life span in mice