Human polymorphonuclear leukocytes produce and express functional tissue factor upon stimulation.
BACKGROUND
Blood-borne tissue factor (TF) plays a crucial role in thrombogenesis.


OBJECTIVE
To study whether polymorphonuclear leukocytes (PMN) are a source of TF.


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 TF:Ag (four to six times), as shown by flow-cytometry and immunocytochemistry. About 40% of permeabilized PMN, both resting and stimulated, contained TF:Ag, indicating that stimulation only modifies the location of TF:Ag 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.
Maugeri
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N
Research Laboratories, Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy. normamaugeri2003@yahoo.it
Brambilla
M
M
Camera
M
M
Carbone
A
A
Tremoli
E
E
Donati
M B
MB
de Gaetano
G
G
Cerletti
C
C
D000911:Antibodies, Monoclonal; D001777:Blood Coagulation; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D019007:P-Selectin / Q000494:pharmacology; D010314:Partial Thromboplastin Time; D021381:Protein Transport; D012333:RNA, Messenger / Q000096:biosynthesis; D013925:Thromboplastin / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D019007:P-Selectin; D012333:RNA, Messenger; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013925:Thromboplastin