caa a22 4500 465764053 CHVBK 20180323111908.0 cr unu---uuuuu 170327e19901201xx s 000 0 eng 10.1007/BF00916371 doi (NATIONALLICENCE)springer-10.1007/BF00916371 Endotoxin-mediated bovine alveolar macrophage procoagulant induction is dependent on protein kinase C activation [Elektronische Daten] [Bruce Car, David Slauson, Monique Doré, M. Suyemoto] The induction of pulmonary alveolar macrophage (PAM) tissue factor-dependent procoagulant activity is central to the deposition of inflammatory fibrin in the pulmonary alveolus. The presence of enhanced tissue factor activity is often associated with pulmonary fibrin deposition, an important pathogenetic event that can delay resolution of pulmonary inflammation and promote the induction of pulmonary fibrosis. Since tissue factor synthesis induction and activation pathways are potential therapeutic targets for modulation of alveolar macrophage tissue factor (procoagulant) activity, we examined the pathways through which endotoxin lipopolysaccharide (LPS) induces bovine PAM tissue factor-dependent procoagulant activity. PAM procoagulant activity was markedly enhanced to 10 times the levels of freshly isolated PAM after 8 h of culture in the presence of either the protein kinase C (PKC) agonist phorbol 12-myristate 13-acetate (PMA) or LPS. Both LPS-(P < 0.002) and PMA-induced activity (P < 0.007) was completely ablated by the PKC inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H 7,100μM but was unaffected by the cyclic nucleotide-dependent protein kinase inhibitorN-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004, 100μM). The arachidonate cyclooxygenase pathway inhibitor phenylbutazone (10−4 M) had modest effects that were not statistically significant. The unstimulated increase of procoagulant activity in 8-h cultures was unaffected by the same inhibitory modulations. These results indicate that PKC-dependent signal transduction pathways are involved in the stimulation of PAM procoagulant activity and that inhibition of this protein kinase prevents LPS-induction of new activity. The results also suggest that the transduction pathways leading to either PMA- or LPS-induced procoagulant activity are similar to the extent that both appear to require an intact PKC system. Plenum Publishing Corporation, 1990 Car Bruce Inflammation Research Laboratory Department of Pathology College of Veterinary Medicine, Cornell University, 14853, Ithaca, New York aut Slauson David Inflammation Research Laboratory Department of Pathology College of Veterinary Medicine, Cornell University, 14853, Ithaca, New York aut Doré Monique Inflammation Research Laboratory Department of Pathology College of Veterinary Medicine, Cornell University, 14853, Ithaca, New York aut Suyemoto M. Inflammation Research Laboratory Department of Pathology College of Veterinary Medicine, Cornell University, 14853, Ithaca, New York aut Inflammation Kluwer Academic Publishers-Plenum Publishers 14/6(1990-12-01), 681-689 0360-3997 14:6<681 1990 14 10753 https://doi.org/10.1007/BF00916371 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00916371 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Car Bruce Inflammation Research Laboratory Department of Pathology College of Veterinary Medicine, Cornell University, 14853, Ithaca, New York aut NATIONALLICENCE 700 1- Slauson David Inflammation Research Laboratory Department of Pathology College of Veterinary Medicine, Cornell University, 14853, Ithaca, New York aut NATIONALLICENCE 700 1- Doré Monique Inflammation Research Laboratory Department of Pathology College of Veterinary Medicine, Cornell University, 14853, Ithaca, New York aut NATIONALLICENCE 700 1- Suyemoto M. Inflammation Research Laboratory Department of Pathology College of Veterinary Medicine, Cornell University, 14853, Ithaca, New York aut NATIONALLICENCE 773 0- Inflammation Kluwer Academic Publishers-Plenum Publishers 14/6(1990-12-01), 681-689 0360-3997 14:6<681 1990 14 10753 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer