Srpski arhiv za celokupno lekarstvo 2010 Volume 138, Issue suppl. 1, Pages: 50-52
https://doi.org/10.2298/SARH10S1050M
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Clinical and experimental evidences on the prothrombotic properties of neutrophils
Maugeri Norma (San Raffaele Scientific Institute and Universitа Vita-Salute San Raffaele, Milano, Italy)
Manfredi Angelo A. (San Raffaele Scientific Institute and Universitа Vita-Salute San Raffaele, Milano, Italy)
Maseri Attilio (San Raffaele Scientific Institute and Universitа Vita-Salute San Raffaele, Milano, Italy)
Epidemiologic studies have shown that the neutrophil count correlates with
the risk of myocardial infarction and stroke and identify patients more
susceptible to reinfarction and in-hospital death. In particular, neutrophils
action was initially associated to blood rheological changes, or to the
effect of neutrophil-derived eicosanoids or proteases. Animal models indicate
that platelet-leukocyte P-selectin dependent cross-talk contributes to fibrin
deposition during in vivo thrombus formation. In fact, platelet P-selectin,
through its leukocyte counter-receptor PSGL-1, determines the activation of
leukocyte β2 integrins, the binding of fibrinogen and the expression of
tissue factor on leukocyte surface. Monocytes stimulated in vitro with LPS,
PMA and P-selectin synthesize and express tissue factor. fMLP, P-selectin,
TNFalpha and C5a are effective stimuli that trigger the synthesis and
expression of biologically active tissue factor in neutrophils. The
experimental evidence well agrees with clinical observations: patients with
acute coronary syndromes, acute respiratory distress syndrome,
antiphospholipid syndromes, giant cell arteritis and myeloproliferative
syndromes have increased the expression of tissue factor on leukocyte
surface. Moreover circulating neutrophils express mRNA codifying for
fulllength and/or alternatively spliced tissue factor, suggesting a new
important link between thrombosis and inflammation. All together, clinical
and experimental evidence suggest that the leukocyte thrombogenic profile is
a relevant player in patients with a high risk of thromboembolic events and
possibly represents a suitable target for molecular intervention.
Keywords: neutrophils, tissue factor, thrombosis, inflammation, arterial thromboembolism