Immunologic mast cell-mediated responses and histamine release are attenuated by heparin.
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 i.v.). 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Lucio
J
J
Division of Pulmonary Disease, Mount Sinai Medical Center, University of Miami School of Medicine, Miami Beach, Florida 33140.
D'Brot
J
J
Guo
C B
CB
Abraham
W M
WM
Lichtenstein
L M
LM
Kagey-Sobotka
A
A
Ahmed
T
T
D000818:Animals; D000947:Antigens, Helminth; D001200:Ascaris / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D006969:Hypersensitivity, Immediate; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D012756:Sheep; D012867:Skin / Q000187:drug effects / Q000276:immunology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000947:Antigens, Helminth; D003189:p-Methoxy-N-methylphenethylamine; D006493:Heparin