Beta2 integrin modulates platelet caspase activation and life span in mice
P F Piguet1, C Vesin, A Rochat
1Department of Pathology, University of Geneva, Switzerland. pierre.piguet@medecine.unige.ch
European Journal of Cell Biology
|April 17, 2001
Summary
The beta2 integrin (CD18) plays a crucial role in mouse platelet function, influencing platelet lifespan and response to inflammation by modulating caspase activation.
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- Platelets are key immune cells involved in hemostasis and inflammation.
- Beta2 integrins, like CD18, are critical for leukocyte adhesion and function.
- The role of CD18 in platelet physiology remains largely unexplored.
Purpose of the Study:
- To investigate the function of CD18 (beta2 integrin) in mouse platelet physiology.
- To determine the impact of CD18 deficiency on platelet lifespan and inflammatory responses.
- To elucidate the molecular mechanisms underlying CD18's role in platelets.
Main Methods:
- Utilized genetically modified mice lacking CD18 (CD18 -/-) or its ligand CD54 (CD54 -/-).
- Assessed platelet CD18 expression and mRNA via immunofluorescence, Western blots, and RT-PCR.
- Evaluated platelet lifespan using in vivo biotinylation and inflammatory localization via intra-tracheal TNF injection.
- Analyzed protein content (Bcl-3, pro-caspase-3, gelsolin) and caspase activity using Western blots, flow cytometry, and protease assays.
Main Results:
- CD18 and CD11a were expressed in wild-type platelets but absent in CD18 -/- platelets.
- Platelets from CD18 -/- mice exhibited a significantly shorter lifespan compared to controls.
- CD18 -/- platelets showed impaired localization to the lung during inflammation.
- Platelets from CD18 -/- mice displayed increased Bcl-3 content, decreased pro-caspase-3, and elevated caspase activation.
- Evidence of caspase-3 cleavage of gelsolin was observed in CD18 -/- platelets.
Conclusions:
- The beta2 integrin CD18 is present and functional in mouse platelets.
- CD18 modulates platelet caspase activation, impacting platelet lifespan.
- CD18 deficiency alters platelet response to inflammatory stimuli like TNF.
- These findings highlight CD18 as a regulator of platelet homeostasis and inflammation.
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