Project: Research project

Project Details


The long-term objective of the proposed studies will be to characterize the
regulation of the synthesis and release of platelet-activating factor
(PAF). From human neutrophilic polymorphonuclear leukocytes (PMN). PAF is
a recently described class of lipid mediator which includes the acetylated
alkyl phosphoglycerides, acetyl glyceryl ether phosphorylcholine (AGEPC).
AGEPC has been shown to be one of the most potent inflammatory mediators
thus far described and possesses a remarkable spectrum of platelet
dependent and independent inflammatory properties, e.g., platelet, PMN and
monocyte stimulation, smooth muscle contraction, and the initiation of
increased vascular permeability. Moreover, PAF is synthesized and released
by PMN, monocytes, platelets, mast cells, basophils, endothelial cells and
likely other cell types strengthening the hypothesis that this lipid
autacoid is involved in normal as well as abnormal inflammatory responses.
Indeed, PAF is now strongly implicated in mediating a variety of
cardiovascular and pulmonary alterations and acute vascular tissue injury.
Thus, alterations in the homeostatic mechanisms regulating both the
synthesis and release of PAF may be a key factor involved in the pathologic
potential of this potent inflammatory mediator. Preliminary evidence now
indicates that the amount and duration of PAF synthesis by FMLP-stimulated
human PMN is tightly coupled to the ability of the PMN to release the
newly-synthesized PAF. However, this hypothesis is based upon the results
of experiments utilizing only FMLP-stimulated PMN. Thus, the proposed
studies will extend these findings and focus upon several intra-and
extracellular factors regulating PAF release from human PMN stimulated with
several physiologically relevent soluble secretagogues and phagocytic
stimuli. Of major emphasis will be the regulation of PAF metabolism by
factors such as divalent cations, albumin and arachidonic acid metabolism.
Hopefully, the results of these studies will provide new and valuable
information for future studies designed to prevent or treat PAF-mediated
inflammatory diseases affecting man.
Effective start/end date12/1/848/31/93


  • National Institutes of Health: $67,743.00


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


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