Human polymorphonuclear leukocytes produce and express functional tissue factor upon stimulation.

ABSTRACT

BACKGROUND: Blood-borne tissue factor (TF) plays a crucial role in thrombogenesis. AIM: To study whether polymorphonuclear leukocytes (PMN) are a source of TF. METHODS AND RESULTS: Human PMN were carefully separated from other blood cells and stimulated for 3 min with purified P-selectin or the chemotactic peptide formyl-MetLeuPhe (fMLP) they expressed both TF procoagulant activity, as identified by specific TF MoAb and inactivated factor VIIa blockade; and TFAg (four to six times), as shown by flow-cytometry and immunocytochemistry. About 40% of permeabilized PMN, both resting and stimulated, contained TFAg, indicating that stimulation only modifies the location of TFAg within PMN. By real time-polymerase chain reaction (RT-PCR), a very low amount of TF mRNA was detectable in resting PMN, but a 3- to 5-fold increase was observed after 1-h stimulation with P-selectin or fMLP, respectively. CONCLUSIONS: These findings suggest that TF is not constitutively expressed in peripheral PMN, but can be up-regulated and produced upon stimulation and specific gene transcription, as for instance during contact with activated platelets or endothelium. The stored TF is rapidly expressed in vitro as a functional molecule on the surface of activated PMN. The availability of PMN TF supports the relevance of inflammatory cells and their interaction with platelets for fibrin deposition and thrombus formation.