Production of platelet-activating factor by stimulated human polymorphonuclear leukocytes

Correlation of synthesis with release, functional events, and leukotriene B4 metabolism

Joseph Harold Sisson, S. M. Prescott, T. M. McIntyre, G. A. Zimmerman

Research output: Contribution to journalArticle

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Abstract

Platelet-activating factor (PAF) is a phospholipid mediator of inflammation that is synthesized by several human cell types including polymorphonuclear leukocytes (PMN). We examined the synthesis and release of PAF by stimulated human PMN under several conditions, assayed by the incorporation of [3H]acetate into PAF and by bioassay. PAF synthesis was induced by calcium ionophore A23187 (IoA), opsonized zymosan (OpsZ), and N-formyl-methionyl-leucyl-phenylalanine (FMLP) with the relative order of potency IoA >> OpsZ > FMLP. A variety of other agonists, including phorbol myristate acetate, an activator of protein kinase C and of PMN functional responses, did not stimulate PAF synthesis. PAF synthesis by PMN in response to IoA, OpsZ, and FMLP was concentration- and time-dependent but release of the phospholipid was not: little PAF (1 to 10%) was released from PMN in suspension regardless of the total amount produced, the agonist, its concentration, the time of incubation, or the concentration of extracellular albumin. This was also the case with functionally altered neutrophils that had been 'primed' with cytochalasin B or lipopolysaccharide or that had adhered to surfaces. PAF synthesis was tightly coupled with leukotriene B4 production by adherent PMN as well as by neutrophils in suspension, supporting the hypothesis that the two lipid autocoids may be derived from a common precursor. However, PAF synthesis could be dissociated from aggregation and surface adhesion, indicating that it is not absolutely required for these responses of activated PMN. The total amount of PAF that accumulated, but not the percentage that was released, was altered in adherent PMN compared to cells in suspension. These experiments demonstrate that PAF production and its subsequent processing by human neutrophils are highly regulated events. PAF synthesis is associated with PMN activation, but it is not a requisite for early adhesive responses of neutrophils. Because little of the PAF produced by stimulated PMN is released from the cells, it appears that PAF has an intracellular role in PMN function and/or that it may have novel intercellular effects that do not require release into the fluid phase.

Original languageEnglish (US)
Pages (from-to)3918-3926
Number of pages9
JournalJournal of Immunology
Volume138
Issue number11
StatePublished - Jan 1 1987

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Leukotriene B4
Platelet Activating Factor
Neutrophils
Zymosan
Calcimycin
methionyl-leucyl-phenylalanine
Suspensions
Ionophores
Phospholipids
N-Formylmethionine Leucyl-Phenylalanine
Inflammation Mediators
Cytochalasin B
Calcium Ionophores
Tetradecanoylphorbol Acetate
Biological Assay
Adhesives
Protein Kinase C

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Production of platelet-activating factor by stimulated human polymorphonuclear leukocytes : Correlation of synthesis with release, functional events, and leukotriene B4 metabolism. / Sisson, Joseph Harold; Prescott, S. M.; McIntyre, T. M.; Zimmerman, G. A.

In: Journal of Immunology, Vol. 138, No. 11, 01.01.1987, p. 3918-3926.

Research output: Contribution to journalArticle

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abstract = "Platelet-activating factor (PAF) is a phospholipid mediator of inflammation that is synthesized by several human cell types including polymorphonuclear leukocytes (PMN). We examined the synthesis and release of PAF by stimulated human PMN under several conditions, assayed by the incorporation of [3H]acetate into PAF and by bioassay. PAF synthesis was induced by calcium ionophore A23187 (IoA), opsonized zymosan (OpsZ), and N-formyl-methionyl-leucyl-phenylalanine (FMLP) with the relative order of potency IoA >> OpsZ > FMLP. A variety of other agonists, including phorbol myristate acetate, an activator of protein kinase C and of PMN functional responses, did not stimulate PAF synthesis. PAF synthesis by PMN in response to IoA, OpsZ, and FMLP was concentration- and time-dependent but release of the phospholipid was not: little PAF (1 to 10{\%}) was released from PMN in suspension regardless of the total amount produced, the agonist, its concentration, the time of incubation, or the concentration of extracellular albumin. This was also the case with functionally altered neutrophils that had been 'primed' with cytochalasin B or lipopolysaccharide or that had adhered to surfaces. PAF synthesis was tightly coupled with leukotriene B4 production by adherent PMN as well as by neutrophils in suspension, supporting the hypothesis that the two lipid autocoids may be derived from a common precursor. However, PAF synthesis could be dissociated from aggregation and surface adhesion, indicating that it is not absolutely required for these responses of activated PMN. The total amount of PAF that accumulated, but not the percentage that was released, was altered in adherent PMN compared to cells in suspension. These experiments demonstrate that PAF production and its subsequent processing by human neutrophils are highly regulated events. PAF synthesis is associated with PMN activation, but it is not a requisite for early adhesive responses of neutrophils. Because little of the PAF produced by stimulated PMN is released from the cells, it appears that PAF has an intracellular role in PMN function and/or that it may have novel intercellular effects that do not require release into the fluid phase.",
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T2 - Correlation of synthesis with release, functional events, and leukotriene B4 metabolism

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N2 - Platelet-activating factor (PAF) is a phospholipid mediator of inflammation that is synthesized by several human cell types including polymorphonuclear leukocytes (PMN). We examined the synthesis and release of PAF by stimulated human PMN under several conditions, assayed by the incorporation of [3H]acetate into PAF and by bioassay. PAF synthesis was induced by calcium ionophore A23187 (IoA), opsonized zymosan (OpsZ), and N-formyl-methionyl-leucyl-phenylalanine (FMLP) with the relative order of potency IoA >> OpsZ > FMLP. A variety of other agonists, including phorbol myristate acetate, an activator of protein kinase C and of PMN functional responses, did not stimulate PAF synthesis. PAF synthesis by PMN in response to IoA, OpsZ, and FMLP was concentration- and time-dependent but release of the phospholipid was not: little PAF (1 to 10%) was released from PMN in suspension regardless of the total amount produced, the agonist, its concentration, the time of incubation, or the concentration of extracellular albumin. This was also the case with functionally altered neutrophils that had been 'primed' with cytochalasin B or lipopolysaccharide or that had adhered to surfaces. PAF synthesis was tightly coupled with leukotriene B4 production by adherent PMN as well as by neutrophils in suspension, supporting the hypothesis that the two lipid autocoids may be derived from a common precursor. However, PAF synthesis could be dissociated from aggregation and surface adhesion, indicating that it is not absolutely required for these responses of activated PMN. The total amount of PAF that accumulated, but not the percentage that was released, was altered in adherent PMN compared to cells in suspension. These experiments demonstrate that PAF production and its subsequent processing by human neutrophils are highly regulated events. PAF synthesis is associated with PMN activation, but it is not a requisite for early adhesive responses of neutrophils. Because little of the PAF produced by stimulated PMN is released from the cells, it appears that PAF has an intracellular role in PMN function and/or that it may have novel intercellular effects that do not require release into the fluid phase.

AB - Platelet-activating factor (PAF) is a phospholipid mediator of inflammation that is synthesized by several human cell types including polymorphonuclear leukocytes (PMN). We examined the synthesis and release of PAF by stimulated human PMN under several conditions, assayed by the incorporation of [3H]acetate into PAF and by bioassay. PAF synthesis was induced by calcium ionophore A23187 (IoA), opsonized zymosan (OpsZ), and N-formyl-methionyl-leucyl-phenylalanine (FMLP) with the relative order of potency IoA >> OpsZ > FMLP. A variety of other agonists, including phorbol myristate acetate, an activator of protein kinase C and of PMN functional responses, did not stimulate PAF synthesis. PAF synthesis by PMN in response to IoA, OpsZ, and FMLP was concentration- and time-dependent but release of the phospholipid was not: little PAF (1 to 10%) was released from PMN in suspension regardless of the total amount produced, the agonist, its concentration, the time of incubation, or the concentration of extracellular albumin. This was also the case with functionally altered neutrophils that had been 'primed' with cytochalasin B or lipopolysaccharide or that had adhered to surfaces. PAF synthesis was tightly coupled with leukotriene B4 production by adherent PMN as well as by neutrophils in suspension, supporting the hypothesis that the two lipid autocoids may be derived from a common precursor. However, PAF synthesis could be dissociated from aggregation and surface adhesion, indicating that it is not absolutely required for these responses of activated PMN. The total amount of PAF that accumulated, but not the percentage that was released, was altered in adherent PMN compared to cells in suspension. These experiments demonstrate that PAF production and its subsequent processing by human neutrophils are highly regulated events. PAF synthesis is associated with PMN activation, but it is not a requisite for early adhesive responses of neutrophils. Because little of the PAF produced by stimulated PMN is released from the cells, it appears that PAF has an intracellular role in PMN function and/or that it may have novel intercellular effects that do not require release into the fluid phase.

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