HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chung, S. W. Articles by Levy, G. A. Search for Related Content PubMed PubMed Citation Articles by Chung, S. W. Articles by Levy, G. A. Agricola Articles by Chung, S. W. Articles by Levy, G. A.

Effect of alterations in early signal transduction events on the induction of procoagulant activity by murine hepatitis virus strain 3 in vitro

The University of Toronto and The Toronto Hospital, Norman Urquhart Wing 10-158, 621 University Avenue, Toronto, Canada M5G 2C4

The induction of macrophage procoagulant activity (PCA) has been shown to correlate with the development of fulminant hepatic necrosis after infection with murine hepatitis virus strain 3 (MHV-3). However, comparatively little is known about the early events in cells after viral infection leading to PCA expression. Accordingly, we investigated the early cellular events in the induction of macrophage PCA by MHV-3. MHV-3 stimulation of macrophages did not result in a detectable increase in intracellular calcium levels nor did stimulation of macrophages by calcium ionophores result in induction of PCA, suggesting that calcium transients were neither necessary nor sufficient for induction of PCA by MHV-3. Treatment of cells with phorbol myristate acetate had no effect on PCA induction; however, inhibition of protein kinase C (PKC) by staurosporine or H7 resulted in attenuation of macrophage PCA following MHV-3 stimulation (P < 0.05 compared with untreated macrophages), suggesting that although activation of PKC alone is insufficient for PCA induction, PKC may be an integral component of PCA induction by MHV-3. We have previously demonstrated that dimethyl prostaglandin E₂ inhibited induction of PCA by MHV-3. In this study, treatment of cells by agents that increase intracellular cAMP (forskolin, isobutylmethyl xanthine) significantly inhibited PCA induction (P < 0.02). These results demonstrate that induction of macrophage PCA by MHV-3 involves PKC, but proceeds independently of changes in intracellular calcium, and that PCA expression is down-regulated by increases in intracellular cAMP.

^* Author for correspondence. Fax +1 416 340 3492. e-mail glevy@torhosp.toronto.on.ca

Received 19 October 1994; accepted 13 December 1994.

This article has been cited by other articles:

				M. A. Makhlouf, L. P. Fernando, T. W. Gettys, P. V. Halushka, and J. A. Cook Increased prostacyclin and PGE2 stimulated cAMP production by macrophages from endotoxin-tolerant rats Am J Physiol Cell Physiol, May 1, 1998; 274(5): C1238 - C1244. [Abstract] [Full Text] [PDF]