Regulation of cytosolic phospholipase A2 phosphorylation and eicosanoid production by colony-stimulating factor 1

Xiangxi Xu, Charles O. Rock, Zhi Hua Qiu, Christina C. Leslie, Suzanne Jackowski

Research output: Contribution to journalArticle

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Abstract

A colony-stimulating factor 1 (CSF-1)-dependent murine macrophage cell line (BAC1.2F5) and peritoneal macrophages were used to investigate the relationship between growth factor-dependent phosphorylation/activation of the 85-kDa cytosolic phospholipase A2 (cPLA2) and arachidonic acid metabolism. The addition of CSF-1 to quiescent BAC1.2F5 cells was followed by the rapid phosphorylation, electrophoretic gel retardation, and stable increase in the specific activity of cPLA2 that correlated with the activation of ERK kinases. cPLA2 phosphorylation depended on the presence of growth factor and persisted throughout the cell cycle. CSF-1 inhibited prostaglandin E2 production and did not enhance arachidonic acid release or increase the levels of lysophosphatidylcholine or glycerophosphocholine. Treatment of BAC1.2F5 cells with the calcium ionophore A23187 plus CSF-1 did not stimulate eicosanoid release. Instead, CSF-1 enhanced the rate of exogenous arachidonic acid incorporation into phosphatidylcholine and its subsequent transfer to phosphatidylethanolamine suggesting that higher rates of arachidonic acid acylation may contribute to the suppression of prostaglandin production. In peritoneal macrophages, ERK kinase activity was stimulated and cPLA2 was phosphorylated and activated in response to CSF-1. However, CSF-1 did not trigger eicosanoid release but did augment arachidonic acid mobilization and prostaglandin E2 production elicited by zymosan and A23187. Thus, cPLA2 phosphorylation/activation and calcium mobilization are not the only determinants for eicosanoid release, and additional components in differentiated tissue macrophages are also required.

Original languageEnglish
Pages (from-to)31693-31700
Number of pages8
JournalJournal of Biological Chemistry
Volume269
Issue number50
StatePublished - Dec 16 1994
Externally publishedYes

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Cytosolic Phospholipases A2
Phosphorylation
Macrophage Colony-Stimulating Factor
Eicosanoids
Arachidonic Acid
Macrophages
Chemical activation
Calcimycin
Peritoneal Macrophages
Dinoprostone
Intercellular Signaling Peptides and Proteins
Phosphotransferases
Cells
Acylation
Lysophosphatidylcholines
Zymosan
Calcium Ionophores
Phosphatidylcholines
Metabolism
Prostaglandins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Regulation of cytosolic phospholipase A2 phosphorylation and eicosanoid production by colony-stimulating factor 1. / Xu, Xiangxi; Rock, Charles O.; Qiu, Zhi Hua; Leslie, Christina C.; Jackowski, Suzanne.

In: Journal of Biological Chemistry, Vol. 269, No. 50, 16.12.1994, p. 31693-31700.

Research output: Contribution to journalArticle

Xu, Xiangxi ; Rock, Charles O. ; Qiu, Zhi Hua ; Leslie, Christina C. ; Jackowski, Suzanne. / Regulation of cytosolic phospholipase A2 phosphorylation and eicosanoid production by colony-stimulating factor 1. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 50. pp. 31693-31700.
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