PMID- 15135804
OWN - NLM
STAT- MEDLINE
DCOM- 20041230
LR  - 20161124
IS  - 1043-4666 (Print)
IS  - 1043-4666 (Linking)
VI  - 26
IP  - 3
DP  - 2004 May 7
TI  - Activated protein C inhibits the release of macrophage inflammatory 
      protein-1-alpha from THP-1 cells and from human monocytes.
PG  - 106-13
AB  - Several lines of evidence have implicated activated protein C (APC) to be an 
      endogenous inhibitor of the inflammatory septic cascade. APC may exhibit direct 
      anti-inflammatory properties, independent of its antithrombotic effects. 
      Chemokines influence the interaction of monocytes at the endothelium during 
      infection and sepsis and are involved in the molecular events leading to an 
      adverse and lethal outcome of sepsis. Defining regulatory mechanisms on the 
      monocytic release profile of the proinflammatory C-C chemokines macrophage 
      inflammatory protein-1-alpha (MIP-1-alpha) and monocyte chemoattractant protein-1 
      (MCP-1) might have therapeutic implications for the treatment of sepsis. We 
      established a monocytic cell model of inflammation by the addition of 
      lipopolysaccharide (LPS) and examined the effect of human APC on LPS-stimulated 
      chemokine release from the monocytic cell line THP-1. We found that human APC in 
      supra-physiological concentrations of 2.5-10 microg/ml inhibited the LPS-induced 
      release of the chemokines MIP-1-alpha and MCP-1, as measured by enzyme-linked 
      immunosorbent assays (ELISA) at 6 up to 24 h. In addition to experiments on THP-1 
      cells, recombinant human APC in concentrations of 50 ng/ml was found to have an 
      inhibiting effect on the release of MIP-1-alpha from freshly isolated mononuclear 
      cells of septic patients. The ability of APC to decrease the release of the C-C 
      chemokine MIP-1-alpha from the monocytic cell line THP-1 and from human monocytes 
      may identify a novel immunomodulatory pathway by which APC exerts its 
      anti-inflammatory action and may contribute to control the inflammatory response 
      in sepsis.
CI  - Copyright 2004 Elsevier Ltd.
FAU - Brueckmann, Martina
AU  - Brueckmann M
AD  - 1st Department of Medicine, Faculty of Clinical Medicine Mannheim, University of 
      Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. 
      martina.brueckmann@med.ma.uni-heidelberg.de
FAU - Hoffmann, Ursula
AU  - Hoffmann U
FAU - De Rossi, Lothar
AU  - De Rossi L
FAU - Weiler, Hans Martin
AU  - Weiler HM
FAU - Liebe, Volker
AU  - Liebe V
FAU - Lang, Siegfried
AU  - Lang S
FAU - Kaden, Jens J
AU  - Kaden JJ
FAU - Borggrefe, Martin
AU  - Borggrefe M
FAU - Haase, Karl K
AU  - Haase KK
FAU - Huhle, Guenter
AU  - Huhle G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Anti-Infective Agents)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (Protein C)
RN  - 0 (Recombinant Proteins)
RN  - JGH8MYC891 (drotrecogin alfa activated)
SB  - IM
MH  - Anti-Infective Agents/pharmacology
MH  - Chemokine CCL4
MH  - Humans
MH  - Macrophage Inflammatory Proteins/*metabolism
MH  - Monocytes/drug effects/*metabolism
MH  - Protein C/*metabolism/pharmacology
MH  - Recombinant Proteins/pharmacology
MH  - Sepsis/drug therapy
EDAT- 2004/05/12 05:00
MHDA- 2004/12/31 09:00
CRDT- 2004/05/12 05:00
PHST- 2003/04/07 00:00 [received]
PHST- 2003/12/22 00:00 [revised]
PHST- 2004/01/27 00:00 [accepted]
PHST- 2004/05/12 05:00 [pubmed]
PHST- 2004/12/31 09:00 [medline]
PHST- 2004/05/12 05:00 [entrez]
AID - S1043466604000420 [pii]
AID - 10.1016/j.cyto.2004.01.004 [doi]
PST - ppublish
SO  - Cytokine. 2004 May 7;26(3):106-13. doi: 10.1016/j.cyto.2004.01.004.