Tissue Factor Expression in Human Neutrophils

Abstract number: P0750

Nakamura¹ S, Okamoto² K, Abumiya³ T

¹¹Department of Cellular Molecular Biology, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8504, Japan ²²Department of Surgery 1, University of Occupational and Environmental Health, Kitakyushu, Japan ³³Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

Tissue factor (TF, CD 142) has a role in functions such as blood coagulation, signal transduction, cell adhesion, and angiogenesis. TF is associated with diseases of DIC, inflammation, atherosclosis, and/or tumor metastasis through these functions. TF expression in leukocytes is of large concern due to its direct connection with above-mentioned diseases and with the origin of blood-borne TF. It is accepted that among leukocytes only monocytes express TF, while neither neutrophils nor lymphocytes do. In a recent paper we reported TF expression in neutrophils based on results in rabbit and monkey [S. Nakamura, et al., JTH, 2:214–6 (2004)]. In our current study we demonstrate further evidences of TF expression in human neutrophils. After incubating normal human blood with LPS, TF mRNA was detected by RT-PCR in purified neutrophils, which were completely depleted of monocytes. In a peritonitis patient, CD15+leukocytes (neutrophils) in peripheral blood and ascites were found to be TF-positive by flow cytometry. A significant amount of TF-positive neutrophils were seen in infiltrated leukocytes at inflamed sites in appendicitis patients. TF-positive neutrophils were also detected in the intra- and intra-microvessel leukocytes in a cerebral enbolism patient. These results provide in vitro and in vivo evidences of de novo production of TF in human neutrophils as well as monocytes. The TF expression appears to be a common neutrophil event among mammals, since its expression was also seen in rabbit and monkey. Because of its apoptotic nature, neutrophil TF appears to be a possible source of TF-bearing circulating microvesicles, the blood-borne TF. There are interesting reports about the association of TF function with cell adhesion, migration, spreading, and intracellular signaling through TF's interaction with ABP-280. These lead us to a tempting hypothesis that TF has a key role in adhesion, transmigration or cell-cell contact of the leukocytes to infiltrate into inflamed sites.