Platelet-activating factor synthesis and phospholipid remodelling in human neutrophils.

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Publication Type dissertation
School or College College of Pharmacy
Department Pharmacology & Toxicology
Author Reinhold, Sandra Lynn.
Title Platelet-activating factor synthesis and phospholipid remodelling in human neutrophils.
Date 1989-08
Description Human neutrophils synthesize platelet-activating factor and leukotriene B4 when exposed to calcium ionophore A23187. The role of protein kinase C in the synthesis of these autacoids was examined. Phorbol 12-myristare-13-acetate (PMA), a direct activator of protein kinase C, did not directly stimulate autacoid synthesis, but enhanced the synthesis of these autacoids in cells stimulated with calcium ionophore A23187. The protein kinase C inhibitors stearoylamine, palmitoylcarnitine, and springosine, prevented A23187-induced PAF and LTB4 synthesis. This inhibition took place at the common step in PAF and LTB4 synthesis: release of their precursors from phospholipid stores via a phospholipase A2-like activity; protein kinase C activity was not required for subsequent metabolism of free arachidonate. A23187 also stimulated incorporation of noneicosanoid-precursor fatty acids into phosphatidylcholine in parallel to its stimulation of PAF synthesis. This was due to the activation of Lands deacylation/reacylation cycle. Deacylation was accomplished by a phospholipase A2 activity that appeared to utilize both diacyl and alkylacyl phosphatidylcholine. The 1-O-alkylglycerophosphocholine (GPC) thus generated was rapidly acetylated by stimulated acyltransferase activity to form PAF. Reacylation of 1-acylGPC, as well as the remaining 1-O-alkylGPC, was accomplished by a stimulated acyltransferase activity that did not employ arachidonylCoA as a substrate. Finally, the regulation of a stimulatable phospholipase D was examined in neutrophils. Protein kinase C activators may activate this enzyme, resulting in the potential generation of second messengers, such as phosphatidic acid, but protein kinase C activation is not required for phospholipase D activity. The fungal metabolite, wortmannin, inhibited receptor-mediated activation of phospholipase D. A model of phospholipase D activation is presented.
Type Text
Publisher University of Utah
Subject Protein Kinase C; Signal Transduction; Immunology
Subject MESH Blood Platelets; Inflammation; Neutrophils; Phospholipase D; Platelet Activating Factor
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of “Platelet-activating factor synthesis and phospholipid remodelling in human neutrophils.” Spencer S. Eccles Health Sciences Library. Print version of “Platelet-activating factor synthesis and phospholipid remodelling in human neutrophils.” available at J. Willard Marriott Library Special Collection. QP6.5 1989 .R44
Rights Management © Sandra Lynn Reinhold.
Format Medium application/pdf
Identifier us-etd2,188
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
ARK ark:/87278/s6183n4c
ID 193384
setname ir_etd
CONTENTdm URL http://cdmbuntu.lib.utah.edu/cdm/ref/collection/etd2/id/1338