PMID- 11807012
OWN - NLM
STAT- MEDLINE
DCOM- 20020306
LR  - 20220311
IS  - 0006-4971 (Print)
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 99
IP  - 3
DP  - 2002 Feb 1
TI  - Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and 
      macrophage adhesion in vivo.
PG  - 1053-9
AB  - Extravascular coagulation leading to fibrin deposition accompanies many immune 
      and inflammatory responses. Although recognized by pathologists for decades, and 
      probably pathologic under certain conditions, the physiologic functions of 
      extravascular coagulation remain to be fully defined. This study demonstrates 
      that thrombin can activate macrophage adhesion and prompt interleukin-6 (IL-6) 
      and monocyte chemoattractant protein-1 (MCP-1) production in vivo. Peritoneal 
      macrophages were elicited with thioglycollate (TG) and then activated in situ, 
      either by intraperitoneal injection of lipopolysaccharide (LPS) or by injection 
      of antigen into mice bearing antigen-primed T cells. Others previously 
      established that such treatments stimulate macrophage adhesion to the mesothelial 
      lining of the peritoneal cavity. The present study demonstrates that thrombin 
      functions in this process, as macrophage adhesion was suppressed by Refludan, a 
      highly specific thrombin antagonist, and induced by direct peritoneal 
      administration of purified thrombin. Although recent studies established that 
      protease activated receptor 1 (PAR-1) mediates some of thrombin's proinflammatory 
      activities macrophage adhesion occurred normally in PAR-1-deficient mice. 
      However, adhesion was suppressed in fibrin(ogen)-deficient mice, suggesting that 
      fibrin formation stimulates macrophage adhesion in vivo. This study also suggests 
      that fibrin regulates chemokine/cytokine production in vivo, as direct injection 
      of thrombin stimulated peritoneal accumulation of IL-6 and MCP-1 in a 
      fibrin(ogen)-dependent manner. Given that prior studies have clearly established 
      inflammatory roles for PAR-1, thrombin probably has pleiotropic functions during 
      inflammation, stimulating vasodilation and mast cell degranulation via PAR-1, and 
      activating cytokine/chemokine production and macrophage adhesion via 
      fibrin(ogen).
FAU - Szaba, Frank M
AU  - Szaba FM
AD  - Trudeau Institute, 100 Algonquin Ave, Saranac Lake, NY 12983, USA.
FAU - Smiley, Stephen T
AU  - Smiley ST
LA  - eng
GR  - R01 HL072937-01/HL/NHLBI NIH HHS/United States
GR  - R01 HL072937-02/HL/NHLBI NIH HHS/United States
GR  - R01 HL072937-04/HL/NHLBI NIH HHS/United States
GR  - R01 HL072937-03/HL/NHLBI NIH HHS/United States
GR  - R01 HL072937/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Caenorhabditis elegans Proteins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-6)
RN  - 9001-32-5 (Fibrinogen)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Animals
MH  - *Caenorhabditis elegans Proteins
MH  - Cell Adhesion/drug effects
MH  - Chemokine CCL2/biosynthesis
MH  - Chemokines/biosynthesis
MH  - Cytokines/biosynthesis/*drug effects
MH  - Disease Models, Animal
MH  - Fibrinogen/genetics/pharmacology/*physiology
MH  - Interleukin-6/biosynthesis
MH  - Macrophages, Peritoneal/*cytology/drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Peritonitis
MH  - Protein Serine-Threonine Kinases/genetics/pharmacology/physiology
MH  - Thrombin/pharmacology/*physiology
PMC - PMC3150214
MID - NIHMS90775
EDAT- 2002/01/25 10:00
MHDA- 2002/03/07 10:01
PMCR- 2011/08/04
CRDT- 2002/01/25 10:00
PHST- 2002/01/25 10:00 [pubmed]
PHST- 2002/03/07 10:01 [medline]
PHST- 2002/01/25 10:00 [entrez]
PHST- 2011/08/04 00:00 [pmc-release]
AID - S0006-4971(20)38302-6 [pii]
AID - 10.1182/blood.v99.3.1053 [doi]
PST - ppublish
SO  - Blood. 2002 Feb 1;99(3):1053-9. doi: 10.1182/blood.v99.3.1053.