PMID- 10586081
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20181016
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 12
DP  - 1999 Dec 15
TI  - Determination of the contribution of cysteinyl leukotrienes and leukotriene B4 in
      acute inflammatory responses using 5-lipoxygenase- and leukotriene A4
      hydrolase-deficient mice.
PG  - 6810-9
AB  - Arachidonic acid metabolism by 5-lipoxygenase leads to production of the potent
      inflammatory mediators, leukotriene (LT) B4 and the cysteinyl LT. Relative
      synthesis of these subclasses of LT, each with different proinflammatory
      properties, depends on the expression and subsequent activity of LTA4 hydrolase
      and LTC4 synthase, respectively. LTA4 hydrolase differs from other proteins
      required for LT synthesis because it is expressed ubiquitously. Also, in vitro
      studies indicate that it possesses an aminopeptidase activity. Introduction of
      cysteinyl LT and LTB4 into animals has shown LTB4 is a potent chemoattractant,
      while the cysteinyl LT alter vascular permeability and smooth muscle tone. It has
      been impossible to determine the relative contributions of these two classes of
      LT to inflammatory responses in vivo or to define possible synergy resulting from
      the synthesis of both classes of mediators. To address this question, we have
      generated LTA4 hydrolase-deficient mice. These mice develop normally and are
      healthy. Using these animals, we show that LTA4 hydrolase is required for the
      production of LTB4 in an in vivo inflammatory response. We show that LTB4 is
      responsible for the characteristic influx of neutrophils accompanying topical
      arachidonic acid and that it contributes to the vascular changes seen in this
      model. In contrast, LTB4 influences only the cellular component of zymosan
      A-induced peritonitis. Furthermore, LTA4 hydrolase-deficient mice are resistant
      to platelet-activating factor, identifying LTB4 as one mediator of the
      physiological changes seen in systemic shock. We do not identify an in vivo role 
      for the aminopeptidase activity of LTA4 hydrolase.
FAU - Byrum, R S
AU  - Byrum RS
AD  - Curriculum in Genetics and Molecular Biology, University of North Carolina,
      Chapel Hill 27599, USA.
FAU - Goulet, J L
AU  - Goulet JL
FAU - Snouwaert, J N
AU  - Snouwaert JN
FAU - Griffiths, R J
AU  - Griffiths RJ
FAU - Koller, B H
AU  - Koller BH
LA  - eng
GR  - P01-DK38108/DK/NIDDK NIH HHS/United States
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  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Inflammation Mediators)
RN  - 0 (Leukotrienes)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Platelet Activating Factor)
RN  - 0 (cysteinyl-leukotriene)
RN  - 1HGW4DR56D (Leukotriene B4)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - I223NX31W9 (Fluorescein-5-isothiocyanate)
RN  - K848JZ4886 (Cysteine)
RN  - V38765PUZ6 (leukotriene A4 hydrolase)
SB  - AIM
SB  - IM
MH  - Acute Disease
MH  - Anaphylaxis/enzymology/genetics/immunology/physiopathology
MH  - Animals
MH  - Arachidonate 5-Lipoxygenase/*deficiency/*genetics
MH  - Arachidonic Acid/physiology
MH  - Cell Movement
MH  - Crosses, Genetic
MH  - Cysteine/*physiology
MH  - Dermatitis, Contact/enzymology/genetics/immunology
MH  - Ear/blood supply/pathology
MH  - Epoxide Hydrolases/*deficiency/*genetics
MH  - Fluorescein-5-isothiocyanate/administration & dosage
MH  - Immunoglobulin E/administration & dosage
MH  - Inflammation Mediators/*physiology
MH  - Leukotriene B4/biosynthesis/*physiology
MH  - Leukotrienes/*physiology
MH  - Lipopolysaccharides/administration & dosage
MH  - Mice
MH  - Mice, Knockout
MH  - Neutrophils/pathology
MH  - Peritonitis/enzymology/*genetics/immunology/physiopathology
MH  - Platelet Activating Factor/administration & dosage
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 - ji_v163n12p6810 [pii]
PST - ppublish
SO  - J Immunol. 1999 Dec 15;163(12):6810-9.