Human granulocyte-macrophage colony-stimulating factor and other cytokines prime human neutrophils for enhanced arachidonic acid release and leukotriene B4 synthesis

J. F. DiPersio, P. Billing, R. Williams, J. C. Gasson

Research output: Contribution to journalArticle

147 Scopus citations

Abstract

Human recombinant granulocyte-macrophage CSF (GM-CSF) 'primes' neutrophils for enhanced biologic responses to a number of secondary stimuli. Here, we examined the properties of neutrophil priming by GM-CSF and other growth factors such as human rTNF and granulocyte CSF. Although GM-CSF has a negligible direct effect on [3H]arachidonic acid release, it enhances or 'primes' neutrophils for three- to fivefold increased release of [3H]arachidonic acid, induced by 1.0 μM A23187 and the chemotactants FMLP, platelet-activating factor, and leukotriene B4 (LTB4) (all 0.1 μM). The priming effects of GM-CSF were concentration- and time-dependent (maximum 100 pM, 1 h at 23°C), and consistent with the determined dissociation constant of the human GM-CSF receptor. Indomethacin (10-6 M), cycloheximide (100 μg/ml), and pertussis toxin (200 ng/ml, 2 h at 37°C) had no effect on GM-CSF-, A23187, or platelet-activating factor-induced [3H]arachidonic acid release. The lipoxygenase inhibitor, nordihydroguaiaretic acid, however, totally abolished A23187-induced [3H]arachidonic acid release from both diluent- and GM-CSF-treated neutrophils. Consistent with this observation, we found that GM-CSF-pretreated neutrophils synthesize increased levels of LTB4 after stimulation with A23187 and chemotactic factors. GM-CSF enhances neutrophil arachidonic acid release and LTB4 synthesis, and thereby may amplify the inflammatory response to chemotactic factors and other physiologically relevant stimuli.

Original languageEnglish
Pages (from-to)4315-4322
Number of pages8
JournalJournal of Immunology
Volume140
Issue number12
StatePublished - Jan 1 1988
Externally publishedYes

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