# BIOTRANSFORMATION OF PLATELET ACTIVATING FACTOR

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 1992 · $113,118

## Abstract

An influx of neutrophils and macrophages characterizes the inflammatory
process.  These cells respond to phagocytic and soluble stimuli by
producing inflammatory mediators including the arachidonic acid metabolites
and platelet activating factor (PAF).  The production of PAF and the
arachidonic acid derived mediators is thought to be very closely related to
the availability of 1-O-alkyl-2-arachidonoyl-sn-glycerol-3-phosphocholine.
This study addresses the contribution made by ether phospholipid catabolism
in the regulation of PAF precursors.

The long term objectives of this proposal are to determine:  1) If the
composition and level of ether phospholipids is regulated, 2) what the
functional significance of this class of phospholipids might be and 3)
elucidate the mechanism of ether phospholipid regulation if such regulation
is found.  The current studies on the metabolism of 1-O-[3H]alkyl-2-acety-
GPC has defined two alternate pathways of PAF metabolism.  A pathway found
in several cell types but represented in this proposal by either bone
marrow derived macrophages or a clonal macrophage-like cell line in which
ethanolamine phospholipids are metabolites of PAF.  The second pathway
found in PC-12 cells (a clonal line derived from rat pheochromocytoma) and
splenic T cells, is characterized by 1-O-alkyl-2-acyl-sn-glycero-3-
phosphoglycerol (1-O-alkyl-2-acyl-GPG) as the primary metabolite.
Surprisingly, the ether linkage of 1-O-alkyl-2-acyl-GPG does not to be
susceptible to hydrolysis.  Studies of PAF metabolism in macrophages
demonstrated that label which originated in the alkyl moiety of 1-O-
[3H]alkyl-2-acetyl-GPC appeared in the following species; 1-O-[3H]alkyl-2-
acetyl-GPC, 1-O-[3H]alkyl-2-acyl-GPC, 1-O-[3H]alkyl-2-acyl-GPE and 1-O-alk-
1'-enyl-2-acyl-GPE after incubations of one hour or less.  After extended
incubation periods (2 to 6 hours) a significant portion of the label was
present in the acyl linkage of diacyl phospholipids and acyl linkage of
neutral lipids indicating then the ether linkage had been cleaved.  A
phsopholilpid base exchange reaction is proposed for the synthesis of 1-O-
alkyl-2-acyl-GPE from 1-O-alkyl-2-acyl-GPC.  The cleavage of the alk-1'-
enyl group of ethanolamine plasmalogen is considered as the means of
releasing the sn-1 group of the ether lipid.

## Key facts

- **NIH application ID:** 3159970
- **Project number:** 5R01AR039742-03
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **SAM.gov UEI:** MW8JHK6ZYEX8
- **Principal Investigator:** RODNEY C. BAKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $113,118
- **Award type:** 5
- **Project period:** 1990-07-06 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159970

## Citation

> US National Institutes of Health, RePORTER application 3159970, BIOTRANSFORMATION OF PLATELET ACTIVATING FACTOR (5R01AR039742-03). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3159970. Licensed CC0.

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