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. 1977 Jun;59(6):1080–1087. doi: 10.1172/JCI108731

Decreased H2 Histamine Response of Granulocytes of Asthmatic Patients

William W Busse 1, Jeffrey Sosman 1
PMCID: PMC372320  PMID: 193871

Abstract

Increased bronchial sensitivity to inhaled histamine in asthma is well known. The mechanism of this increased bronchial sensitivity is not known nor has it been demonstrated that isolated cells respond abnormally to histamine. Polymorpho-nuclear leukocytes (PMNs) provide a homogeneous cell population to study agonist response. Release of granulocyte lysosomal enzymes is inhibited by agonists increasing the PMN cyclic AMP concentration. The release of the lysosomal enzyme beta glucuronidase by serum-activated particles of zymosan was similar in PMNs isolated from normal and asthma subjects. Histamine (100-0.01 μM) inhibited enzyme release. Except at the maximal concentration of histamine (100 μM), the response to histamine was decreased in asthma. The inhibition of enzyme release paralleled an increase in intracellular PMN cyclic AMP. In asthma, the cyclic AMP response to histamine was reduced. The H2 antihistamine metiamide blocked histamine inhibition of lysosomal enzyme release and the increase in cyclic AMP. The effect was maximal at concentrations equimolar to those of histamine. The H1 antihistamine chlorpheniramine had no effect on histamine inhibition of granulocyte lysosomal enzyme release. A decrease in the inhibition of the release of the inflammatory lysosomal enzymes from granulocytes in asthma may contribute to an enhanced bronchial inflammatory reaction.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ash A. S., Schild H. O. Receptors mediating some actions of histamine. Br J Pharmacol Chemother. 1966 Aug;27(2):427–439. doi: 10.1111/j.1476-5381.1966.tb01674.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bach M. A. Differences in Cyclic AMP Changes after Stimulation by Prostaglandins and Isoproterenol in Lymphocyte Subpopulations. J Clin Invest. 1975 May;55(5):1074–1081. doi: 10.1172/JCI108008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Black J. W., Duncan W. A., Durant C. J., Ganellin C. R., Parsons E. M. Definition and antagonism of histamine H 2 -receptors. Nature. 1972 Apr 21;236(5347):385–390. doi: 10.1038/236385a0. [DOI] [PubMed] [Google Scholar]
  4. Bourne H. R., Melmon K. L., Lichtenstein L. M. Histamine augments leukocyte adenosine 3',5'-monophosphate and blocks antigenic histamine release. Science. 1971 Aug 20;173(3998):743–745. doi: 10.1126/science.173.3998.743. [DOI] [PubMed] [Google Scholar]
  5. Brown B. L., Albano J. D., Ekins R. P., Sgherzi A. M. A simple and sensitive saturation assay method for the measurement of adenosine 3':5'-cyclic monophosphate. Biochem J. 1971 Feb;121(3):561–562. doi: 10.1042/bj1210561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Busse W. W., Sosman J. Histamine inhibition of neutrophil lysosomal enzyme release: an H2 histamine receptor response. Science. 1976 Nov 12;194(4266):737–738. doi: 10.1126/science.185696. [DOI] [PubMed] [Google Scholar]
  7. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  8. CABAUD P. G., WROBLEWSKI F. Colorimetric measurement of lactic dehydrogenase activity of body fluids. Am J Clin Pathol. 1958 Sep;30(3):234–236. doi: 10.1093/ajcp/30.3.234. [DOI] [PubMed] [Google Scholar]
  9. Curry J. J. COMPARATIVE ACTION OF ACETYL-BETA-METHYL CHOLINE AND HISTAMINE ON THE RESPIRATORY TRACT IN NORMALS, PATIENTS WITH HAY FEVER, AND SUBJECTS WITH BRONCHIAL ASTHMA. J Clin Invest. 1947 May;26(3):430–438. doi: 10.1172/JCI101826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eyre P. Histamine H2-receptors in the sheep bronchus and cat trachea: the action of burimamide. Br J Pharmacol. 1973 Jun;48(2):321–323. doi: 10.1111/j.1476-5381.1973.tb06920.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fishman W. H., Kato K., Anstiss C. L., Green S. Human serum beta-glucuronidase; its measurement and some of its properties. Clin Chim Acta. 1967 Mar;15(3):435–447. doi: 10.1016/0009-8981(67)90008-3. [DOI] [PubMed] [Google Scholar]
  12. Gillespie E., Valentine M. D., Lichtenstein L. M. Cyclic AMP metabolism in asthma: studies with leukocytes and lymphocytes. J Allergy Clin Immunol. 1974 Jan;53(1):27–33. doi: 10.1016/0091-6749(74)90096-7. [DOI] [PubMed] [Google Scholar]
  13. Henson P. M. The immunologic release of constituents from neutrophil leukocytes. I. The role of antibody and complement on nonphagocytosable surfaces or phagocytosable particles. J Immunol. 1971 Dec;107(6):1535–1546. [PubMed] [Google Scholar]
  14. Ignarro L. J., Colombo C. Enzyme release from polymorphonuclear leukocyte lysosomes: regulation by autonomic drugs and cyclic nucleotides. Science. 1973 Jun 15;180(4091):1181–1183. doi: 10.1126/science.180.4091.1181. [DOI] [PubMed] [Google Scholar]
  15. KIND L. S. The altered reactivity of mice after inoculation with Bordetella pertussis vaccine. Bacteriol Rev. 1958 Sep;22(3):173–182. doi: 10.1128/br.22.3.173-182.1958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kaliner M., Orange R. P., Austen K. F. Immunological release of histamine and slow reacting substance of anaphylaxis from human lung. J Exp Med. 1972 Sep 1;136(3):556–567. doi: 10.1084/jem.136.3.556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kirkpatrick C. H., Keller C. Impaired responsiveness to epinephrine in asthma. Am Rev Respir Dis. 1967 Oct;96(4):692–699. doi: 10.1164/arrd.1967.96.4.692. [DOI] [PubMed] [Google Scholar]
  18. Lichtenstein L. M., Gillespie E. Inhibition of histamine release by histamine controlled by H2 receptor. Nature. 1973 Aug 3;244(5414):287–288. doi: 10.1038/244287a0. [DOI] [PubMed] [Google Scholar]
  19. Lichtenstein L. M., Margolis S. Histamine release in vitro: inhibition by catecholamines and methylxanthines. Science. 1968 Aug 30;161(3844):902–903. doi: 10.1126/science.161.3844.902. [DOI] [PubMed] [Google Scholar]
  20. Lockey S. D., Jr, Glennon J. A., Reed C. E. Comparison of some metabolic responses in normal and asthmatic subjects to epinephrine and glucagon. J Allergy. 1967 Dec;40(6):349–354. doi: 10.1016/0021-8707(67)90024-x. [DOI] [PubMed] [Google Scholar]
  21. Logsdon P. J., Middleton E., Jr, Coffey R. G. Stimulation of leukocyte adenyl cyclase by hydrocortisone and isoproterenol in asthmatic and nonasthmatic subjects. J Allergy Clin Immunol. 1972 Jul;50(1):45–56. doi: 10.1016/0091-6749(72)90078-4. [DOI] [PubMed] [Google Scholar]
  22. MCNEILL R. S. EFFECT OF A BETA-ADRENERGIC-BLOCKING AGENT, PROPRANOLOL, ON ASTHMATICS. Lancet. 1964 Nov 21;2(7369):1101–1102. doi: 10.1016/s0140-6736(64)92617-0. [DOI] [PubMed] [Google Scholar]
  23. Mathé A. A., Volicer L., Puri S. K. Effect of anaphylaxis and histamine, pyrilamine and burimamide on levels of cyclic AMP and cyclic GMP in guinea-pig lung. Res Commun Chem Pathol Pharmacol. 1974 Aug;8(4):635–651. [PubMed] [Google Scholar]
  24. Middleton E., Jr, Finke S. R. Metabolic response to epinephrine in bronchial asthma. J Allergy. 1968 Nov;42(5):288–299. doi: 10.1016/0021-8707(68)90022-1. [DOI] [PubMed] [Google Scholar]
  25. Newball H. H., Keiser H. R. Relative effects of bradykinin and histamine on the respiratory system of man. J Appl Physiol. 1973 Oct;35(4):552–556. doi: 10.1152/jappl.1973.35.4.552. [DOI] [PubMed] [Google Scholar]
  26. PARKER C. D., BILBO R. E., REED C. E. METHACHOLINE AEROSOL AS TEST FOR BRONCHIAL ASTHMA. Arch Intern Med. 1965 Apr;115:452–458. doi: 10.1001/archinte.1965.03860160078013. [DOI] [PubMed] [Google Scholar]
  27. Parker C. W., Smith J. W. Alterations in cyclic adenosine monophosphate metabolism in human bronchial asthma. I. Leukocyte responsiveness to -adrenergic agents. J Clin Invest. 1973 Jan;52(1):48–59. doi: 10.1172/JCI107173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. SZENTIVANYI A., FISHEL C. W., TALMAGE D. W. ADRENALINE MEDIATION OF HISTAMINE AND SEROTONIN HYPERGLYCEMIA IN NORMAL MICE AND THE ABSENCE OF ADRENALINE-INDUCED HYPERGLYCEMIA IN PERTUSSIS-SENSITIZED MICE. J Infect Dis. 1963 Sep-Oct;113:86–98. doi: 10.1093/infdis/113.2.86. [DOI] [PubMed] [Google Scholar]
  29. Sullivan T. J., Parker K. L., Eisen S. A., Parker C. W. Modulation of cyclic AMP in purified rat mast cells. II. Studies on the relationship between intracellular cyclic AMP concentrations and histamine release. J Immunol. 1975 May;114(5):1480–1485. [PubMed] [Google Scholar]
  30. Weissmann G., Zurier R. B., Spieler P. J., Goldstein I. M. Mechanisms of lysosomal enzyme release from leukocytes exposed to immune complexes and other particles. J Exp Med. 1971 Sep 1;134(3 Pt 2):149s–165s. [PubMed] [Google Scholar]
  31. Zaid G., Beall G. N. Bronchial response to beta-adrenergic blockade. N Engl J Med. 1966 Sep 15;275(11):580–584. doi: 10.1056/NEJM196609152751103. [DOI] [PubMed] [Google Scholar]
  32. Zurier R. B., Hoffstein S., Weissmann G. Cytochalasin B: effect on lysosomal enzyme release from human leukocytes. Proc Natl Acad Sci U S A. 1973 Mar;70(3):844–848. doi: 10.1073/pnas.70.3.844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Zurier R. B., Weissmann G., Hoffstein S., Kammerman S., Tai H. H. Mechanisms of lysosomal enzyme release from human leukocytes. II. Effects of cAMP and cGMP, autonomic agonists, and agents which affect microtubule function. J Clin Invest. 1974 Jan;53(1):297–309. doi: 10.1172/JCI107550. [DOI] [PMC free article] [PubMed] [Google Scholar]

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