Diesel exhaust particles impair platelet response to collagen and are associated with GPIb[alpha] shedding

Marc Forestier, Mohammad Al-Tamimi, Elizabeth Ellen Gardiner, Corinna Hermann, Sara C Meyer, Jurg Hans Beer

Research output: Contribution to journalArticleResearchpeer-review

9 Citations (Scopus)

Abstract

Air pollution with fine particulates (PM 10 and PM 2.5) is associated with an increased incidence of cardiovascular events. The proposed mechanisms include indirect proinflammatory and procoagulant reactions involving activation of pulmonary macrophages, endothelial cells and the TNF/TF pathway, or direct procoagulant effects. Our laboratory has observed a reduction of the platelet responsiveness to collagen after exposure to diesel exhaust particles (DEP). Hypothesis: DEP directly interfere with platelet-collagen interactions by selectively inducing the shedding of platelet signaling receptors via metalloproteinases, which would represent a novel mechanism for DEP action on platelets. Methods: Citrated blood from healthy volunteers was exposed to highly standardized DEP at concentrations of 0.1, 2.5 and 5.0 I?g/ml or ultrafine carbon black (ufCB, 0.1 I?g/ml) and the plasmatic and platelet response was analysed. The closure times with the PFA-100 device and the platelet aggregation in response to a variety of agonists were monitored. Interleukins (IL)-1I? and IL-8 levels were determined by ELISA and soluble P-selectin by the Luminex bead assay. Thrombin activity was measured as the endogenous thrombin potential (ETP) by fluorescence spectrometry. Soluble GPVI and GPIbI? (glycocalicin) ectodomain fragments were measured by ELISA. ADAMTS13 activity was determined by a FRETS based assay and plasmin activity with Spectrozyme PL. Results: Aggregation assays where platelets were treated with low dose DEP or ultrafine carbon black (ufCB) revealed a significantly increased response to low doses of collagen (p<0.05, n= 5). At higher doses, however, collagen induced aggregation was suppressed by DEP treatment: at 2.5 I?g/ml, the inhibition was 34 A? 12 (p<0.01, n= 10). Aggregations with cross-linked collagen related peptide (CRPxl), convulxin and with the monoclonal antibody 9O12.2 (all known to specifically bind to and activate GPVI) were also diminished. Risto
Original languageEnglish
Pages (from-to)930 - 938
Number of pages9
JournalToxicology in Vitro
Volume26
Issue number6
DOIs
Publication statusPublished - 2012

Cite this