Platelet Abnormalities during Colonic Inflammation

Yan S. L. S., Russell J., Harris N. R., Senchenkova E. Y., YILDIRIM A., Granger D. N.

INFLAMMATORY BOWEL DISEASES, cilt.19, sa.6, ss.1245-1253, 2013 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 19 Sayı: 6
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1097/mib.0b013e318281f3df
  • Dergi Adı: INFLAMMATORY BOWEL DISEASES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1245-1253
  • Anahtar Kelimeler: thrombocytosis, platelet activation, platelet-leukocyte aggregation, selectins, immature platelets, IN-VIVO BIOTINYLATION, PROTEIN-C PATHWAY, BOWEL-DISEASE, RETICULATED PLATELETS, P-SELECTIN, EXTRAINTESTINAL MANIFESTATIONS, NEUTROPHIL, THROMBOSIS, COLITIS, MOUSE
  • Marmara Üniversitesi Adresli: Hayır

Özet

Patients with inflammatory bowel disease are susceptible to microvascular thrombosis and thromboembolism. The increased incidence of thrombosis is accompanied by enhanced coagulation and abnormalities in platelet function. Clinical studies have revealed thrombocytosis, alterations in platelet activation, enhanced platelet-leukocyte interactions, and elevated plasma levels of prothrombotic cytokines. This study was directed toward determining whether the thrombocytosis, altered platelet functions, and enhanced platelet-leukocyte interactions observed in patients with inflammatory bowel disease can be recapitulated in the dextran sodium sulfate and T-cell transfer models of murine colonic inflammation. Flow cytometry was used to characterize platelet function in heparin-anticoagulated whole blood of control mice and in mice with colonic inflammation. Platelets were identified by characteristic light scattering and membrane expression of CD41. Thiazole orange labeling was used to differentiate between immature and mature platelets. Platelet activation was monitored using the expression of an activation epitope of GPIIb/IIIa integrin. The combination of CD41, CD45.2, Gr-1, F4/80, and isotype control antibodies was used to detect and quantify aggregates of leukocytes, neutrophils, and monocytes with platelets. Our results indicated that colonic inflammation is associated with thrombocytosis, leukocytosis, and the appearance of immature platelets. An increased number of circulating activated platelets was detected in colitic mice, along with the formation of aggregates of leukocytes (PLA), neutrophils (PNA), and monocytes (PMA) with platelets. Selectin blockade with fucoidin inhibited dextran sodium sulfate-induced PLA formation. The findings of this study indicate that many features of the altered platelet function detected in human inflammatory bowel disease can be reproduced in animal models of colonic inflammation.