Transcellular metabolism of neutrophil-derived leukotriene A4 by human platelets. A potential cellular source of leukotriene C4
Transformation of leukotriene (LT) A4 into leukotriene C4 has been found to be carried out by human platelets in a rather efficient manner. LTC4 was characterized by a combination of high performance liquid chromatography, UV spectrophotometry, use of labeled precursor, guinea pig ileum bioassay, and enzyme immunoassay. LTA4 metabolism was found to be substrate-dependent, time-dependent, and proportional to platelet concentration even at sub- or supraphysiological levels (0.0019-1 X 10(9) platelets/ml). Neither plasma alone nor the supernatant of resting or activated platelets was found to catalyze the production of LTC4 in the presence or in the absence of reduced glutathione. These data suggest that platelets contain a glutathione S-transferase specific for LTC4 biosynthesis. The formation of LTC4 was greatly enhanced when LTA4 was incubated with platelets in the presence of albumin. Low concentrations of albumin (2-4 g/liter) stabilized LTA4 to an extent that conversion into LTC4 by the platelets could be detected after 1 h of incubation. The possible intercellular transfer of LTA4 between neutrophils and platelets was tested. The production of LTC4 by neutrophils was greatly enhanced in the presence of platelets. Furthermore, the supernatant of neutrophils stimulated with the calcium ionophore contained a short-lived acid-labile substance which was converted by the platelets into LTC4. When platelets were prelabeled with (/sup 35/S)cysteine to allow intracellular synthesis of (/sup 35/S)glutathione, the coincubation of both cell types challenged with the calcium ionophore resulted in the production of (/sup 35/S) LTC4.
- Research Organization:
- Univ. of Colorado Health Sciences Center, Denver
- OSTI ID:
- 5513879
- Journal Information:
- J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 263:1; ISSN JBCHA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ALBUMINS
AMINO ACIDS
ANIMALS
ARACHIDONIC ACID
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOASSAY
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD PLATELETS
BODY FLUIDS
CARBOXYLIC ACIDS
CHROMATOGRAPHY
CYSTEINE
DAYS LIVING RADIOISOTOPES
DRUGS
ENZYME IMMUNOASSAY
EVEN-ODD NUCLEI
FUNCTIONS
GLUTATHIONE
IMMUNOASSAY
ISOTOPE APPLICATIONS
ISOTOPES
LEUKOCYTES
LIGHT NUCLEI
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MAN
MATERIALS
METABOLISM
MONOCARBOXYLIC ACIDS
NEUTROPHILS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PEPTIDES
POLYPEPTIDES
PRIMATES
PROTEINS
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
SEPARATION PROCESSES
SPECTRA
SULFUR 35
SULFUR ISOTOPES
THIOLS
TIME DEPENDENCE
TRACER TECHNIQUES
ULTRAVIOLET SPECTRA
VERTEBRATES