IgE-dependent activation of cytokine-primed mouse cultured mast cells induces a delayed phase of prostaglandin D2 generation via prostaglandin endoperoxide synthase-2

M. Murakami, Clifton Bingham, R. Matsumoto, K. F. Austen, J. P. Arm

Research output: Contribution to journalArticle

Abstract

Mouse hone marrow-derived mast cells (BMMC) developed with IL-3 generate prostaglandin D2 (PGD2) through the utilization of prostaglandin endoperoxide synthase (PGHS)-1 within several minutes of cross-linking the high affinity Fc receptor for IgE (FcεRI) by hapten-specific IgE and Ag. We now report that this immediate generation of PGD2 is followed by a 15-fold induction of steady-state transcripts for PGHS-2, with a maximum at 30 min, accompanied by transient expression of PGHS-2 protein. When BMMC were pretreated with c-kit ligand (KL) in combination with IL-10 for 2 h, sensitized with IgE, and activated with Ag, their expression of steady-state transcripts for PGHS-2 increased 111-fold and their expression of PGHS-2 protein was markedly enhanced, with maximal expression at 1 h and 5 h, respectively, after activation. These events were accompanied by PGD2 generation from 1 to 10 h after activation that accounted for approximately 50% of total PGD2 generation. The expression of PGHS-1 protein did not change during this period. The optimal priming interval for the effect of KL plus IL-10 on the IgE-dependent induction of PGHS-2 was 2 h, at which time only this particular cytokine combination acted synergistically with activation by IgE and Ag. In contrast, at 2 days the accessory cytokines that could provide priming with KL included IL-3 and IL-9 in addition to IL-10. Dexamethasone, which inhibited the expression of PGHS-2 but not PGHS-1, and NS-398, a selective inhibitor of PGHS-2, each suppressed the delayed phase but not the immediate phase of PGD2 generation. Conversely, valeryl salicylate, a selective inhibitor of PGHS-1, suppressed the immediate but not the delayed phase of PGD2 generation after cell priming and IgE-dependent activation.

Original languageEnglish (US)
Pages (from-to)4445-4453
Number of pages9
JournalJournal of Immunology
Volume155
Issue number9
StatePublished - 1995
Externally publishedYes

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Prostaglandin D2
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
Mast Cells
Immunoglobulin E
Cultured Cells
Cytokines
Stem Cell Factor
Interleukin-10
Interleukin-3
Interleukin-9
Proteins
Fc Receptors
Salicylates
Haptens
Dexamethasone
Interleukin-2
Bone Marrow

ASJC Scopus subject areas

  • Immunology

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IgE-dependent activation of cytokine-primed mouse cultured mast cells induces a delayed phase of prostaglandin D2 generation via prostaglandin endoperoxide synthase-2. / Murakami, M.; Bingham, Clifton; Matsumoto, R.; Austen, K. F.; Arm, J. P.

In: Journal of Immunology, Vol. 155, No. 9, 1995, p. 4445-4453.

Research output: Contribution to journalArticle

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abstract = "Mouse hone marrow-derived mast cells (BMMC) developed with IL-3 generate prostaglandin D2 (PGD2) through the utilization of prostaglandin endoperoxide synthase (PGHS)-1 within several minutes of cross-linking the high affinity Fc receptor for IgE (FcεRI) by hapten-specific IgE and Ag. We now report that this immediate generation of PGD2 is followed by a 15-fold induction of steady-state transcripts for PGHS-2, with a maximum at 30 min, accompanied by transient expression of PGHS-2 protein. When BMMC were pretreated with c-kit ligand (KL) in combination with IL-10 for 2 h, sensitized with IgE, and activated with Ag, their expression of steady-state transcripts for PGHS-2 increased 111-fold and their expression of PGHS-2 protein was markedly enhanced, with maximal expression at 1 h and 5 h, respectively, after activation. These events were accompanied by PGD2 generation from 1 to 10 h after activation that accounted for approximately 50{\%} of total PGD2 generation. The expression of PGHS-1 protein did not change during this period. The optimal priming interval for the effect of KL plus IL-10 on the IgE-dependent induction of PGHS-2 was 2 h, at which time only this particular cytokine combination acted synergistically with activation by IgE and Ag. In contrast, at 2 days the accessory cytokines that could provide priming with KL included IL-3 and IL-9 in addition to IL-10. Dexamethasone, which inhibited the expression of PGHS-2 but not PGHS-1, and NS-398, a selective inhibitor of PGHS-2, each suppressed the delayed phase but not the immediate phase of PGD2 generation. Conversely, valeryl salicylate, a selective inhibitor of PGHS-1, suppressed the immediate but not the delayed phase of PGD2 generation after cell priming and IgE-dependent activation.",
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