CELLULAR PATHWAYS OF LIPOXYGENATION OF ARACHIDONIC ACID

Project: Research project

Project Details

Description

The mediators of hypersensitivity and inflammation generated by cellular
enzymatic pathways of lipoxygenation of arachidonic acid have been defined
structurally and in terms of their potent effects on human airway smooth
muscles, blood vessels, epithelial cells, glands, nerves, phagocytic
leukocytes, and T-lymphocytes. The research proposed will focus on the
central biochemical and cellular events critical to the activation and
regulation of expression of specific lipoxygenases and related cellular
enzymes. The physician-scientist training of the principal investigator
will begin with a broad education (Phase I) in the chemistry and
immunochemistry of eicosanoids and other fatty acids, the cell biology and
enzymology of the lipoxygenation of fatty acids, the differentiation and
functions of enzymes, receptors and other cellular structures, and the
molecular genetics and biochemistry of biological macromolecules. The
concepts and laboratory methods assimilated then will be applied by the
principal investigator in a program of research (Phase II) designed to
elucidate the characteristics of development of lipoxygenases and epoxide
hydrolases in the course of differentiation of cultured human and animal
mast cells and eosinophils. The products of lipoxygenation of arachidonic
acid will be identified and quantified by chromatographic, spectrometric,
and radioimmunochemical techniques in studies of the time-course, cellular
properties, and specific stimuli of the development of lipoxygenases and
epoxide hydrolases. The 5-lipoxygenase and 5,6-epoxide hydrolase of mast
cells and the 15-lipoxygenase and 14,15-epoxide hydrolase of eosinophils
will be purified and the catalytic activities, specificity, and
susceptibility of the purified enzymes to natural and pharmacological
modulation will be defined. A biologically relevant lipoxygenase will be
selected for purification in quantities sufficient for determinations of
structural and molecular genetic properties. The elucidation of the
cellular and chemical bases for development and activation of the pathways
of lipoxygenation of arachidonic acid will lead to more reliable assays for
detection of abnormalities in the pathways in defective host defense and in
immunological diseases and to the development of more specific agents for
effective treatment of such disorders.
StatusFinished
Effective start/end date9/1/858/31/90

Funding

  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

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