PMID- 8704250
OWN - NLM
STAT- MEDLINE
DCOM- 19960912
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 88
IP  - 3
DP  - 1996 Aug 1
TI  - Tumor necrosis factor-alpha induces activation of coagulation and fibrinolysis in 
      baboons through an exclusive effect on the p55 receptor.
PG  - 922-7
AB  - Tumor necrosis factor-alpha (TNF-alpha) can bind to two distinct transmembrane 
      receptors, the p55 and p75 TNF receptors. We compared the capability of two 
      mutant TNF proteins with exclusive affinity for the p55 or p75 TNF receptor with 
      that of wild type TNF, to activate the hemostatic mechanism in baboons. Both 
      activation of the coagulation system, monitored by the plasma levels of 
      thrombin-antithrombin III complexes, and activation of the fibrinolytic system 
      (plasma levels of tissue-type plasminogen activator, and plasminogen activator 
      inhibitor type I), were of similar magnitude after intravenous injection of wild 
      type TNF or the TNF mutant with affinity only for the p55 receptor. Likewise, 
      wild type TNF and the TNF p55 specific mutant were equally potent in inducing 
      neutrophil degranulation (plasma levels of elastase-alpha 1-antitrypsin 
      complexes). Wild type TNF tended to be a more potent inducer of secretory 
      phospholipase A2 release than the p55 specific TNF mutant. Administration of the 
      TNF mutant binding only to the p75 receptor did not induce any of these 
      responses. We conclude that TNF-Induced stimulation of coagulation, fibrinolysis, 
      neutrophil degranulation, and release of secretory phospholipase A2 are 
      predominantly mediated by the p55 TNF receptor.
FAU - van der Poll, T
AU  - van der Poll T
AD  - Cornell University Medical College, Laboratory of Surgical Metabolism, New York, 
      NY 10021, USA.
FAU - Jansen, P M
AU  - Jansen PM
FAU - Van Zee, K J
AU  - Van Zee KJ
FAU - Welborn, M B 3rd
AU  - Welborn MB 3rd
FAU - de Jong, I
AU  - de Jong I
FAU - Hack, C E
AU  - Hack CE
FAU - Loetscher, H
AU  - Loetscher H
FAU - Lesslauer, W
AU  - Lesslauer W
FAU - Lowry, S F
AU  - Lowry SF
FAU - Moldawer, L L
AU  - Moldawer LL
LA  - eng
GR  - GM-34695/GM/NIGMS NIH HHS/United States
GR  - GM-40586-07/GM/NIGMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Phospholipases A2)
RN  - EC 3.4.21.36 (Pancreatic Elastase)
RN  - EC 3.4.21.37 (Leukocyte Elastase)
SB  - IM
MH  - Animals
MH  - Antigens, CD/*drug effects/physiology
MH  - Blood Coagulation/*drug effects/physiology
MH  - Fibrinolysis/*drug effects/physiology
MH  - Leukocyte Elastase
MH  - Mutagenesis, Site-Directed
MH  - Neutrophils/drug effects/enzymology
MH  - Pancreatic Elastase/metabolism
MH  - Papio/blood
MH  - Phospholipases A/metabolism
MH  - Phospholipases A2
MH  - Point Mutation
MH  - Receptors, Tumor Necrosis Factor/*drug effects/physiology
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Receptors, Tumor Necrosis Factor, Type II
MH  - Recombinant Proteins/pharmacology
MH  - Substrate Specificity
MH  - Tumor Necrosis Factor-alpha/genetics/*pharmacology
EDAT- 1996/08/01 00:00
MHDA- 2001/03/28 10:01
CRDT- 1996/08/01 00:00
PHST- 1996/08/01 00:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1996/08/01 00:00 [entrez]
AID - S0006-4971(20)62517-4 [pii]
PST - ppublish
SO  - Blood. 1996 Aug 1;88(3):922-7.