Beta2 integrin modulates platelet caspase activation and life span in mice.
We explored the role of CD18 (beta2 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 beta2 integrin, present in mouse platelets, modulates caspase activation and consequently platelet life span and response to TNF.
Piguet
P F
PF
Department of Pathology, University of Geneva, Switzerland. pierre.piguet@medecine.unige.ch
Vesin
C
C
Rochat
A
A
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000081242:B-Cell Lymphoma 3 Protein; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D015153:Blotting, Western; D018821:CD18 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002448:Cell Adhesion; D004789:Enzyme Activation; D018260:Gelsolin / Q000378:metabolism; D015870:Gene Expression; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017304:Annexin A5; D000081242:B-Cell Lymphoma 3 Protein; C000631345:Bcl3 protein, mouse; D018821:CD18 Antigens; D018260:Gelsolin; D016169:Lymphocyte Function-Associated Antigen-1; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases