PMID- 10589939
OWN - NLM
STAT- MEDLINE
DCOM- 19991221
LR  - 20190713
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 68
IP  - 10
DP  - 1999 Nov 27
TI  - Neutrophil elastase and oxygen radicals enhance monocyte chemoattractant protein- 
      expression after ischemia/reperfusion in rat liver.
PG  - 1459-68
AB  - BACKGROUND: The monocyte chemoattractant protein-1 (MCP-1) is produced during 
      reperfusion injury and induces tissue factor that is the initiator of the 
      clotting cascade. Neutrophil elastase is a crucial mediator of inflammatory 
      tissue damage. Activation of the coagulation system stimulates cytokine 
      production by activated leukocytes. We investigated the effects of neutrophil 
      elastase and oxygen radicals generated by hypoxia associated with microthrombus 
      formation on MCP-1 expression after ischemia/reperfusion in rat liver. METHODS: 
      In vitro MCP-1 production by macrophages after stimulation with human neutrophil 
      elastase (HNE) or oxygen radicals generated by hypoxanthine and xanthine oxidase 
      was examined. Liver ischemia was induced in rats by occluding the portal vein for 
      30 min. An inhibitor of human neutrophil elastase (ONO-5046*Na, 10 mg/kg) and 
      antithrombin III (AT-III, 250 U/kg) were injected i.v. 5 min before vascular 
      clamping. Serum concentrations of MCP-1 were measured by enzyme-linked 
      immunosorbent assay. RESULTS: Human neutrophil elastase or oxygen radicals 
      significantly enhanced in vitro MCP-1 production by macrophage. Serum MCP-1 
      concentrations reached a peak at 6 hr after reperfusion and then gradually 
      decreased. However, pretreatment of animals with AT-III or ONO-5046*Na alone 
      resulted in significantly smaller increases in serum concentrations of MCP-1 
      after reperfusion. Pretreatment with both ONO-5046*Na and AT-III produced 
      additive effects. The combined treatment with ONO-5046*Na and AT-III 
      significantly reduced MCP-1 mRNA in liver after ischemia/reperfusion. 
      CONCLUSIONS: MCP-1 production by macrophages is stimulated by neutrophil elastase 
      and oxygen radicals generated by hypoxia, probably due to microthrombus formation 
      after ischemia/reperfusion of the rat liver.
FAU - Yamaguchi, Y
AU  - Yamaguchi Y
AD  - Department of Surgery II, Kumamoto University Medical School, Japan.
FAU - Matsumura, F
AU  - Matsumura F
FAU - Liang, J
AU  - Liang J
FAU - Okabe, K
AU  - Okabe K
FAU - Ohshiro, H
AU  - Ohshiro H
FAU - Ishihara, K
AU  - Ishihara K
FAU - Matsuda, T
AU  - Matsuda T
FAU - Mori, K
AU  - Mori K
FAU - Ogawa, M
AU  - Ogawa M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Chemokine CCL2)
RN  - 0 (Serine Proteinase Inhibitors)
RN  - 0 (Sulfonamides)
RN  - 11062-77-4 (Superoxides)
RN  - 9000-94-6 (Antithrombin III)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - DWI62G0P59 (sivelestat)
RN  - EC 3.4.21.37 (Leukocyte Elastase)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Animals
MH  - Antithrombin III/pharmacology
MH  - Cell Hypoxia
MH  - Cells, Cultured
MH  - Chemokine CCL2/blood/*genetics
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gene Expression Regulation
MH  - Glycine/analogs & derivatives/pharmacology
MH  - Humans
MH  - Hydrogen Peroxide/pharmacology
MH  - Ischemia/*metabolism
MH  - Kupffer Cells/drug effects/metabolism
MH  - Leukocyte Elastase/antagonists & inhibitors/*metabolism/pharmacology
MH  - Liver/*blood supply/*metabolism
MH  - Macrophages, Peritoneal/drug effects/metabolism
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - *Reperfusion
MH  - Serine Proteinase Inhibitors/pharmacology
MH  - Sulfonamides/pharmacology
MH  - Superoxides/*pharmacology
MH  - Transcription, Genetic
EDAT- 1999/12/10 00:00
MHDA- 1999/12/10 00:01
CRDT- 1999/12/10 00:00
PHST- 1999/12/10 00:00 [pubmed]
PHST- 1999/12/10 00:01 [medline]
PHST- 1999/12/10 00:00 [entrez]
AID - 10.1097/00007890-199911270-00005 [doi]
PST - ppublish
SO  - Transplantation. 1999 Nov 27;68(10):1459-68. doi: 
      10.1097/00007890-199911270-00005.