In vitro and in vivo model systems for the study of allergic and inflammatory disorders in man. Implications for the pathogenesis of asthma

S. P. Peters, R. M. Naclerio, A. Togias, R. P. Schelimer, Donald Macglashan, A. Kagey-Sobotka, N Franklin Adkinson, Philip S. Norman, L. M. Lichtenstein

Research output: Contribution to journalArticle

Abstract

Recently we have studied arachidonic acid metabolism in human mast cells and have shown that cells prelabeled with 3H-arachidonic acid display phospholipid remodeling (arachidonic acid is lost from phosphotidylcholine and phosphotidylinositol) and metabolize released arachidonic acid by both cyclooxygenase and lipoxygenase enzymes. The major cyclooxygenase metabolite produced by purified human lung mast cells is prostaglandin D2, the major lipoxygenase product produced by these cells is leukotriene C4, with smaller amounts of leukotriene B isomers and 5-hydroxyeicosatetranoic acid (5 HETE) also observed. While the human basophil is very similar to the mast cell in that it also contains significant amounts of histamine and generates large quantities of leukotriene C4 after activation, it is different in that it generates little or no prostaglandin D2. Both cell types apparently have the ability to secrete proteins with kininogenase and TAME (tosyl arginine methyl ester)-esterase enzymatic activities. Mast cells and basophils also differ in their response to pharmacologic agents. The human basophil responds to indomethacin and the lipoxygenase product 5 HPETE by increasing the release of both histamine and leukotriene C after antigen triggering; the mast cell does not. Incubation of the human basophil overnight in the presence of dexamethasone results in a marked reduction in the amount of histamine and leukotriene C4 released from these cells, while similar treatment of the human lung mast cells does not affect histamine release, prostaglandin D2 release or the release of slow-reacting substance of anaphylaxis.

Original languageEnglish (US)
JournalChest
Volume87
Issue number5 SUPPL.
StatePublished - 1985

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Mast Cells
Leukotriene C4
Asthma
Basophils
Prostaglandin D2
Arachidonic Acid
Lipoxygenase
Histamine Release
Prostaglandin-Endoperoxide Synthases
Histamine
SRS-A
Arachidonate Lipoxygenases
Lung
Kallikreins
Leukotriene B4
Esterases
Indomethacin
Dexamethasone
In Vitro Techniques
Phospholipids

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Peters, S. P., Naclerio, R. M., Togias, A., Schelimer, R. P., Macglashan, D., Kagey-Sobotka, A., ... Lichtenstein, L. M. (1985). In vitro and in vivo model systems for the study of allergic and inflammatory disorders in man. Implications for the pathogenesis of asthma. Chest, 87(5 SUPPL.).

In vitro and in vivo model systems for the study of allergic and inflammatory disorders in man. Implications for the pathogenesis of asthma. / Peters, S. P.; Naclerio, R. M.; Togias, A.; Schelimer, R. P.; Macglashan, Donald; Kagey-Sobotka, A.; Adkinson, N Franklin; Norman, Philip S.; Lichtenstein, L. M.

In: Chest, Vol. 87, No. 5 SUPPL., 1985.

Research output: Contribution to journalArticle

Peters, S. P. ; Naclerio, R. M. ; Togias, A. ; Schelimer, R. P. ; Macglashan, Donald ; Kagey-Sobotka, A. ; Adkinson, N Franklin ; Norman, Philip S. ; Lichtenstein, L. M. / In vitro and in vivo model systems for the study of allergic and inflammatory disorders in man. Implications for the pathogenesis of asthma. In: Chest. 1985 ; Vol. 87, No. 5 SUPPL.
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AU - Schelimer, R. P.

AU - Macglashan, Donald

AU - Kagey-Sobotka, A.

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