Document Detail

Enhancement of delayed hypersensitivity inflammatory reactions in guinea pig skin by 12(R)-hydroxy-5,8,14-eicosatrienoic acid.
MedLine Citation:
PMID:  7798640     Owner:  NLM     Status:  MEDLINE    
Delayed-type hypersensitivity (DTH) reactions are initiated by sensitized T cells. Their progression is dependent upon the local release of various autacoids, including cytokines and eicosanoids, by T cells, infiltrating inflammatory cells, and resident tissue cells. 12(R)-hydroxy-5,8,14-eicosatrienoic acid [12(R)-HETrE], an eicosanoid produced by skin and cornea, possesses potent proinflammatory properties at picomolar concentrations including vasodilation, increase in membrane permeability, neutrophil chemotaxis, and angiogenesis. Because DTH reactions are associated with many of these same phenomena, we examined the effect of 12(R)-HETrE and related 12-hydroxyeicosanoids on the expression of DTH to purified protein derivative of tuberculin in sensitized guinea pigs. In the absence of purified protein derivative of tuberculin, none of the eicosanoids evoked erythema or edema after intradermal injection at doses up to 100 pmol. When injected together with purified protein derivative of tuberculin, 12(R)-hydroxy-5,8,10,14-eicosatetraenoic acid [12(R)-HETE], but not its enantiomer 12(S)-HETE, significantly inhibited macroscopic expression of delayed reactivity (erythema) only at the highest dose tested, 10 pmol. In contrast, 12(R)-HETrE significantly enhanced expression of DTH at doses between 1 fmol and 1 pmol (50% and 30% increases above control, respectively). Its stereoisomer, 12(S)-HETrE, did not enhance DTH at any tested dose, but was able to block the activity of 12(R)-HETrE when injected simultaneously. Enhancement or inhibition of visible skin responses was not associated with qualitative or quantitative changes in cellular infiltrates at the reaction site. 12(R)-HETrE had no effect on the nonimmunologic inflammatory skin reaction induced by phorbol myristate acetate, suggesting selectivity toward DTH. We conclude that 12(R)-HETrE enhances DTH via a yet to be determined mechanism and that its stereoisomer, 12(S)-HETrE, may be a useful antagonist for studying the inflammatory actions of this eicosanoid.
M S Conners; M L Schwartzman; X Quan; E Heilman; K Chauhan; J R Falck; H P Godfrey
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  104     ISSN:  0022-202X     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  1995 Jan 
Date Detail:
Created Date:  1995-01-24     Completed Date:  1995-01-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  47-51     Citation Subset:  IM    
Department of Pharmacology, New York Medical College, Valhalla 10595.
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MeSH Terms
8,11,14-Eicosatrienoic Acid / analogs & derivatives*,  pharmacology
Capillary Permeability / drug effects
Dermatitis / immunology
Erythema / etiology,  immunology,  physiopathology
Guinea Pigs
Hypersensitivity, Delayed / physiopathology*
Skin / drug effects*,  immunology*
Tetradecanoylphorbol Acetate / pharmacology
Tuberculin / immunology
Grant Support
Reg. No./Substance:
0/Tuberculin; 117346-20-0/12-hydroxy-5,8,14-eicosatrienoic acid; 16561-29-8/Tetradecanoylphorbol Acetate; 7324-41-6/8,11,14-Eicosatrienoic Acid

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