title: Recombinant human thrombomodulin inhibits neutrophil extracellular trap formation in vitro.
abstract: The aim of this study was to investigate the effects of recombinant human-soluble thrombomodulin (rTM) on lipopolysaccharide (LPS)-induced, platelet-dependent neutrophil extracellular trap (NET) formation (NETosis). Human peripheral blood neutrophils and platelets were co-incubated with or without LPS (0.2 μg/ml) in the presence and absence of rTM (2 μg/ml). NETosis was confirmed by immunostaining and confocal microscopy. In the absence of platelets, LPS did not induce NETosis in the neutrophils. NETosis, however, was induced by LPS when neutrophils were co-cultured with platelets (64 % of neutrophils). Notably, rTM was able to fully inhibit NETosis in neutrophils cultured with platelets and in the presence of LPS. rTM did not induce NETosis in this co-culture system (p < 0.01 versus LPS in the absence of rTM). These results show that rTM can suppress LPS-induced platelet-dependent NETosis in vitro.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Shimomura
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Suga
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192 Japan ; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, MA 02129 USA.
authors.forename: Naohide
authors.initials: N
authors.lastname: Kuriyama
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hara
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Chizuru
authors.initials: C
authors.lastname: Yamashita
authors.affiliation: Department of Physiology I, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192 Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagasaki
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, MA 02129 USA.
authors.forename: Masao
authors.initials: M
authors.lastname: Kaneki
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nishida
keywords: Disseminated intravascular coagulation; Innate immunity; Neutrophil extracellular traps; Sepsis; Thrombomodulin