Decreased H2 Histamine Response of Granulocytes of Asthmatic Patients

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1977 Jun 1

PMID 193871

Citations 9

Authors

W W Busse

J Sosman

Affiliations

Soon will be listed here.

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 muM) inhibited enzyme release. Except at the maximal concentration of histamine (100 muM), 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.

Citing Articles

Molecular and cellular analysis of human histamine receptor subtypes.

Seifert R, Strasser A, Schneider E, Neumann D, Dove S, Buschauer A Trends Pharmacol Sci. 2012; 34(1):33-58.

PMID: 23254267 PMC: 3869951. DOI: 10.1016/j.tips.2012.11.001.

Effect of inhaled H1 and H2 receptor antagonist in normal and asthmatic subjects.

Thomson N, Kerr J Thorax. 1980; 35(6):428-34.

PMID: 6449094 PMC: 471304. DOI: 10.1136/thx.35.6.428.

Dimaprit inhibition of zymosan-stimulated beta-glucuronidase release from human granulocytes.

Busse W, Cooper W, Anderson C Agents Actions. 1980; 10(1 Pt 2):15-8.

PMID: 6446228 DOI: 10.1007/BF02024173.

Inhibition of IgE-mediated histamine release from human leukocytes by a new xanthine derivative, D 4026.

Petersson B, Svedinger I, Bohlinder K Agents Actions. 1980; 10(5):403-10.

PMID: 6163338 DOI: 10.1007/BF01968037.

Beta adrenergic receptors of polymorphonuclear particulates in bronchial asthma.

Galant S, Duriseti L, Underwood S, Allred S, Insel P J Clin Invest. 1980; 65(3):577-85.

PMID: 6101600 PMC: 371398. DOI: 10.1172/JCI109702.

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