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

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 microM A23187 and the chemotactants FMLP, platelet-activating factor, and leukotriene B4 (LTB4) (all 0.1 microM). The priming effects of GM-CSF were concentration- and time-dependent (maximum 100 pM, 1 h at 23 degrees C), and consistent with the determined dissociation constant of the human GM-CSF receptor. Indomethacin (10(-8) M), cycloheximide (100 micrograms/ml), and pertussis toxin (200 ng/ml, 2 h at 37 degrees 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.

• Publication year

  1988

• Venue

  Journal of Immunology

• Publication date

  1988-06-15

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.4049/jimmunol.140.12.4315PMID 2453577
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• The lipoxygenase inhibitor nordihydroguaiaretic acid completely abolishes A23187-induced arachidonic acid release from both untreated and GM-CSF-treated neutrophils.

  Confidence 0.90

  All you need is Python (5d7gwfm5zu) extraction뀨 (7c402c1b98) reviewAnonymous (12632b8b5f) review
• The priming effect of GM-CSF on arachidonic acid release is concentration- and time-dependent, with a maximum effect observed at 100 pM over 1 hour at 23 degrees C.

  Confidence 0.90

  All you need is Python (5d7gwfm5zu) extraction뀨 (7c402c1b98) reviewAnonymous (12632b8b5f) review
• GM-CSF primes neutrophils to increase arachidonic acid release and leukotriene B4 synthesis when stimulated by secondary agents such as A23187, FMLP, platelet-activating factor, and LTB4.

  Confidence 0.95

  All you need is Python (5d7gwfm5zu) extraction뀨 (7c402c1b98) reviewAnonymous (12632b8b5f) review

• a23187

  reagent, molecule

  A calcium ionophore used as a chemical stimulus to induce arachidonic acid release.

  All you need is Python (5d7gwfm5zu) extraction뀨 (7c402c1b98) reviewAnonymous (12632b8b5f) review
• arachidonic acid

  molecule

  A polyunsaturated fatty acid released from cells during inflammatory responses.

  Aliases: [3H]arachidonic acid

  All you need is Python (5d7gwfm5zu) extraction뀨 (7c402c1b98) reviewAnonymous (12632b8b5f) review
• gm-csf

  cytokine, protein

  A human cytokine and growth factor studied for its priming effects on immune cells.

  Aliases: granulocyte-macrophage CSF

  All you need is Python (5d7gwfm5zu) extraction뀨 (7c402c1b98) reviewAnonymous (12632b8b5f) review
• leukotriene b4

  lipid mediator, molecule

  A lipid mediator involved in inflammation that is synthesized from arachidonic acid.

  Aliases: LTB4

  All you need is Python (5d7gwfm5zu) extraction뀨 (7c402c1b98) reviewAnonymous (12632b8b5f) review
• neutrophils

  cell type

  A type of human white blood cell examined for its inflammatory response to cytokines.

  Aliases: human neutrophils

  All you need is Python (5d7gwfm5zu) extraction뀨 (7c402c1b98) reviewAnonymous (12632b8b5f) review
• priming

  biological process

  The enhancement of a cell's response to a secondary stimulus following pretreatment with a cytokine.

  Aliases: neutrophil priming

  All you need is Python (5d7gwfm5zu) extraction뀨 (7c402c1b98) reviewAnonymous (12632b8b5f) review

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