Raised Plasma Soluble P-Selectin in Peripheral Arterial Occlusive Disease Enhances Leukocyte Adhesion

K.J. Woollard, D. Kling, S. Kulkarni, A.M. Dart, S. Jackson, J. Chin-Dusting
2006 Circulation Research  
Raised levels of soluble P-selectin (sP-selectin) have been reported in the plasma of patients with vascular diseases; however, the functional importance of this ligand remains unclear. In this study we have examined a potential role for plasma sP-selectin in regulating neutrophil adhesion in patients with peripheral arterial occlusive disease (PAOD). Patients with PAOD had significantly higher levels of sP-selectin (meanϮSD: 73.3Ϯ13.0 versus 16.7Ϯ6.4 ng/mL) and enhanced whole blood leukocyte
more » ... e blood leukocyte adhesion to platelets under shear. To examine whether the raised sP-selectin levels can directly influence leukocyte adhesion, isolated neutrophils were incubated with plasma from PAOD patients before and after immunodepletion of sP-selectin. Neutrophil adhesion to fibrinogen increased 2-fold following incubation with PAOD plasma, which was abrogated on sP-selectin immunodepletion. We subsequently demonstrated that recombinant sP-selectin dose-dependently (75 to 250 ng/mL) increased leukocyte adhesion to fibrinogen and platelet monolayers. This increase was PSGL-1 and Src kinase-dependent and correlated with an increase in sP-selectin-mediated Mac-1 activation. sP-selectin-stimulated neutrophil adhesion to platelet monolayers was inversely correlated with shear, such that at low shear (50 s Ϫ1 ) a 92.7%Ϯ15.7 increase in adhesion was observed decreasing to 38.5%Ϯ11.9 at 150 s Ϫ1 and 10.1%Ϯ7.4 at 300 s Ϫ1 . These studies suggest a potentially important role for sP-selectin in modulating neutrophil adhesion in patients with PAOD, particularly at sites of low shear, where it raises the possibility that raised plasma sP-selectin levels may enhance leukocyte recruitment to vascular injury and promote disease progression. (Circ Res. 2006;98:0-0.)
doi:10.1161/01.res.0000199295.14073.69 pmid:16339486 fatcat:3nwmykbk2fcxzfnfhoylxfomxa