Premium
Primary and secondary capture of platelets in the femoral artery are mediated by P‐selectin and PSGL‐1 in vivo
Author(s) -
Braun Oscar Östberg,
Slotta Jan,
Erlinge David,
Thorlacius Henrik
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a18-a
Subject(s) - platelet , in vivo , intravital microscopy , p selectin , chemistry , platelet adhesiveness , adhesion , platelet activation , femoral artery , lipopolysaccharide , immunology , microbiology and biotechnology , medicine , biology , platelet aggregation , organic chemistry
The mechanistic explanation of platelet‐endothelial and platelet‐leukocyte‐endothelial interactions in large vessels in vivo is not fully elucidated. Studies so far have focused on platelet interactions in the microcirculation such as postcapillary venules or interactions in vitro. We used intravital fluorescence microscopy of the femoral artery in C57/BL6 mice to study primary and secondary capture of platelets onto endothelial cells as well as onto adherent platelets and leukocytes in vivo. By use of monoclonal antibodies, the role of P‐selectin and PSGL‐1 in these adhesive interactions in mice exposed to lipopolysaccharide (LPS) was determined. Intravenous challenge with LPS increased platelet tethering to 40.5 ± 9.8, rolling to 20.5 ± 6.2 and adhesion to 147.0 ± 35.7 platelets/mm 2 in the femoral artery (P < 0.01 vs. PBS treated control, n = 8–14). Moreover, secondary capture of platelets to adherent platelets increased to 16.2 ± 7.7 and secondary platelet capture onto adherent leukocytes increased to 15.2±7.0 platelets/mm 2 . Notably, pretreatment with the anti‐PSGL‐1 antibody decreased platelet tethering to 6.4 ± 2.6, rolling to 2.5 ± 2.0 and adhesion to 6.3 ± 6.3 platelets/mm 2 (P < 0.05 vs. control antibody+LPS, n = 8–14). Immunoneutralization of P‐selectin decreased platelet tethering to 5.0 ± 2.9, rolling to 0.5 ± 0.5 and adhesion to 5.0 ± 5.0 platelets/mm2 (P < 0.01 vs. control antibody+LPS, n = 8–14). In addition, inhibition of P‐selectin and PSGL‐1 completely abolished secondary capture of platelets onto adherent platelets and leukocytes. In conclusion, our data show that primary and secondary capture of platelets in the femoral artery are critically dependent of P‐selectin and PSGL‐1 in vivo.