| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Center for Blood Research and
Surgical Research Laboratories, Children’s Hospital, Harvard Medical School, Boston, MA 02115
C1 inhibitor (C1INH) is beneficial in animal models of endotoxemia and sepsis. However, the mechanism(s) of C1INH protection remain(s) ill-defined. In this study, we demonstrated that both active C1INH and reactive center-cleaved, inactive C1INH protected mice from lethal Gram-negative endotoxemia. Both forms of C1INH blocked the LPS-binding protein-dependent binding of Salmonella typhimurium LPS to the murine macrophage cell line, RAW 264.7, and suppressed LPS-induced TNF-
mRNA expression. Inhibition of LPS binding to RAW 264.7 cells was reversed with anti-C1INH Ab and was more efficient when C1INH was incubated first with LPS rather than with the cells. C1INH also suppressed LPS-induced up-regulation of TNF- mRNA in whole human blood. The interaction of C1INH with LPS was directly demonstrated both by ELISA and by nondenaturing PAGE, but deletion of the amino-terminal 97-aa residues abrogated this binding. Therefore, C1INH, in addition to its function as a serine protease inhibitor, has a novel anti-inflammatory function mediated via its heavily glycosylated amino-terminal non-serpin domain.
This article has been cited by other articles:
|
|
 |
|
  F. Lu, A. K. Chauhan, S. M. Fernandes, M. T. Walsh, D. D. Wagner, and A. E. Davis III The effect of C1 inhibitor on intestinal ischemia and reperfusion injury Am J Physiol Gastrointest Liver Physiol, November 1, 2008; 295(5): G1042 - G1049. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Liu, F. Lu, G. Qin, S. M. Fernandes, J. Li, and A. E. Davis III C1 Inhibitor-Mediated Protection from Sepsis J. Immunol., September 15, 2007; 179(6): 3966 - 3972. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Beinrohr, V. Harmat, J. Dobo, Z. Lorincz, P. Gal, and P. Zavodszky C1 Inhibitor Serpin Domain Structure Reveals the Likely Mechanism of Heparin Potentiation and Conformational Disease J. Biol. Chem., July 20, 2007; 282(29): 21100 - 21109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Liu, C. C. Cramer, J. Scafidi, and A. E. Davis III N-Linked Glycosylation at Asn3 and the Positively Charged Residues within the Amino-Terminal Domain of the C1 Inhibitor Are Required for Interaction of the C1 Inhibitor with Salmonella enterica Serovar Typhimurium Lipopolysaccharide and Lipid A Infect. Immun., August 1, 2005; 73(8): 4478 - 4487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Liu, D. Zhang, J. Scafidi, X. Wu, C. C. Cramer, and A. E. Davis III C1 inhibitor prevents Gram-negative bacterial lipopolysaccharide-induced vascular permeability Blood, March 15, 2005; 105(6): 2350 - 2355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Kang, Y. D. Yoon, I. J. Cho, M. H. Han, C. W. Lee, S.-K. Park, and H. M. Kim Glabridin, an Isoflavan from Licorice Root, Inhibits Inducible Nitric-Oxide Synthase Expression and Improves Survival of Mice in Experimental Model of Septic Shock J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 1187 - 1194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Liu, X. Gu, J. Scafidi, and A. E. Davis III N-Linked Glycosylation Is Required for C1 Inhibitor-Mediated Protection from Endotoxin Shock in Mice Infect. Immun., April 1, 2004; 72(4): 1946 - 1955. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
