Immunologic mast cell-mediated responses and histamine release are attenuated by heparin

J. Lucio, J. D'Brot, C. B. Guo, W. M. Abraham, L. M. Lichtenstein, A. Kagey-Sobotka, T. Ahmed

Research output: Contribution to journalArticle

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Abstract

Heparin has been shown to act as a competitive inhibitor of inositol 1,4,5-triphosphate (InsP3) receptors in various cell types. Because InsP3 is one of the second messengers involved in stimulus-secretion coupling in mast cells, it is possible that heparin may inhibit mast cell-mediated reactions. Therefore, in allergic sheep, we tested this hypothesis in two mast cell-mediated reactions induced by immunologic and nonimmunologic stimuli: immediate cutaneous reaction (ICR) and acute bronchoconstrictor response (ABR). In 12 sheep allergic to Ascaris suum antigen, the surface area of the skin wheal was determined 20 min after intradermal injection (0.05 ml) of increasing concentrations of specific antigen, compound 48/80, and histamine, without and after pretreatment with heparin (100, 300, or 1,000 U/kg iv). Antigen, compound 48/80, and histamine produced concentration-dependent increases in ICR. Heparin 'partially' inhibited the ICR to antigen and compound 48/80 in a dose-dependent manner without modifying the ICR to histamine. The heparin preservative benzyl alcohol was ineffective. In 11 additional sheep, specific lung resistance was measured before and after inhalation challenges with antigen, compound 48/80, and histamine without and with aerosol heparin pretreatment (1,000 U/kg). Heparin blocked the antigen- and compound 48/80-induced bronchoconstriction without modifying the airway effects of histamine. In isolated human uterine mast cells, heparin inhibited the anti-immunoglobulin E- but not the calcium ionophore- (A23187) induced histamine release. These data suggest that heparin inhibits the ICR and ABR induced by stimuli that produce immunologic and nonimmunologic mast cell degranulation without attenuating the effects of histamine. This action of heparin may be due to modulation of mast cell mediator release rather than to inhibition of end organ receptor sites involved in these reactions.

Original languageEnglish
Pages (from-to)1093-1101
Number of pages9
JournalJournal of Applied Physiology
Volume73
Issue number3
StatePublished - Jan 1 1992
Externally publishedYes

Fingerprint

Histamine Release
Mast Cells
Heparin
p-Methoxy-N-methylphenethylamine
Histamine
Skin
Antigens
Bronchoconstrictor Agents
Sheep
Ascaris suum
Benzyl Alcohol
Inositol 1,4,5-Trisphosphate Receptors
Cell Degranulation
Intradermal Injections
Bronchoconstriction
Calcium Ionophores
Calcimycin
Second Messenger Systems
Surface Antigens
Aerosols

Keywords

  • antigen
  • compound 48/80
  • inositol 1,4,5-triphosphate

ASJC Scopus subject areas

  • Endocrinology
  • Physiology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Lucio, J., D'Brot, J., Guo, C. B., Abraham, W. M., Lichtenstein, L. M., Kagey-Sobotka, A., & Ahmed, T. (1992). Immunologic mast cell-mediated responses and histamine release are attenuated by heparin. Journal of Applied Physiology, 73(3), 1093-1101.

Immunologic mast cell-mediated responses and histamine release are attenuated by heparin. / Lucio, J.; D'Brot, J.; Guo, C. B.; Abraham, W. M.; Lichtenstein, L. M.; Kagey-Sobotka, A.; Ahmed, T.

In: Journal of Applied Physiology, Vol. 73, No. 3, 01.01.1992, p. 1093-1101.

Research output: Contribution to journalArticle

Lucio, J, D'Brot, J, Guo, CB, Abraham, WM, Lichtenstein, LM, Kagey-Sobotka, A & Ahmed, T 1992, 'Immunologic mast cell-mediated responses and histamine release are attenuated by heparin', Journal of Applied Physiology, vol. 73, no. 3, pp. 1093-1101.
Lucio J, D'Brot J, Guo CB, Abraham WM, Lichtenstein LM, Kagey-Sobotka A et al. Immunologic mast cell-mediated responses and histamine release are attenuated by heparin. Journal of Applied Physiology. 1992 Jan 1;73(3):1093-1101.
Lucio, J. ; D'Brot, J. ; Guo, C. B. ; Abraham, W. M. ; Lichtenstein, L. M. ; Kagey-Sobotka, A. ; Ahmed, T. / Immunologic mast cell-mediated responses and histamine release are attenuated by heparin. In: Journal of Applied Physiology. 1992 ; Vol. 73, No. 3. pp. 1093-1101.
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