Activated monocytes capture platelets for heterotypic association in patients with severe carotid artery stenosis

Thromb Haemost. 2010 Jun;103(6):1193-202. doi: 10.1160/TH09-09-0620. Epub 2010 Mar 29.

Abstract

Inflammation and thrombosis, two processes influencing each other, are involved in the pathogenesis of cerebrovascular disease. We showed that in patients with acute ischaemic stroke circulating platelets are activated and exhausted. To identify whether activated haemostasis might be cause or effect, we investigated the role of leukocyte and platelet activation in patients with severe asymptomatic and symptomatic carotid artery disease. Flow cytometry analysis demonstrated that monocytes from symptomatic (acute stroke aetiology) and asymptomatic patients were highly activated, shown by significantly enhanced presentation of inflammatory markers CD11b and thrombospondin-1 (TSP-1) on the surface. Both correlated positively with monocyte-platelet association rate. However, increased monocyte activation and elevated levels of monocyte-platelet associates in asymptomatic patients were restricted to patients with echo-lucent plaques, providing a close link between monocyte activation and plaque morphology. Circulating single as well as monocyte-bound platelets from symptomatic patients showed significantly enhanced surface expression of P-selectin and TSP-1, whereas platelets from asymptomatic patients were not significantly activated. These results indicate that monocytes activated by inflammation rather than platelets might be the candidates to initiate platelet-monocyte rosetting during the pathogenesis of atherothrombotic cerebral ischaemia and that haemostasis might be activated secondarily by the first occurring inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / metabolism
  • Blood Platelets / immunology
  • Blood Platelets / metabolism
  • Blood Platelets / pathology
  • CD11b Antigen / metabolism
  • Carotid Stenosis / diagnosis*
  • Carotid Stenosis / pathology*
  • Carotid Stenosis / physiopathology
  • Cell Separation
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • Humans
  • Inflammation
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Monocytes / metabolism*
  • Monocytes / pathology
  • P-Selectin / genetics
  • P-Selectin / metabolism
  • Platelet Activation
  • Stroke
  • Thrombospondin 1 / metabolism

Substances

  • Biomarkers
  • CD11b Antigen
  • P-Selectin
  • Thrombospondin 1