HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Chhabra, J. Articles by Hughes, J. M. Search for Related Content PubMed PubMed Citation Articles by Chhabra, J. Articles by Hughes, J. M.

Histamine and tryptase modulate asthmatic airway smooth muscle GM-CSF and RANTES release

¹ Respiratory Research Group, Faculty of Pharmacy, and ² Dept of Pharmacology, University of Sydney, Sydney, NSW, Australia, ³ These authors contributed equally to the preparation of the manuscript.

CORRESPONDENCE: J. M. Hughes, Faculty of Pharmacy A15, University of Sydney, Sydney NSW 2006, Australia. Fax: 61 293514391. E-mail: margh{at}pharm.usyd.edu.au

Keywords: Airway smooth muscle, asthma, granulocyte-macrophage colony-stimulating factor, histamine, RANTES, tryptase

Received: August 14, 2006
Accepted January 22, 2007

Degranulating mast cells are increased in the airway smooth muscle (ASM) of asthmatics, where they may influence ASM function. The aim of the present study was to determine whether histamine and tryptase modulate ASM cell granulocyte-macrophage colony-stimulating factor (GM-CSF) and RANTES (regulated on activation, normal T-cell expressed and secreted) release and also to examine which receptors are involved in this release.

Confluent, quiescent ASM cells from asthmatic and nonasthmatic donors were treated with histamine (1 µM–100 µM) with and without histamine receptor antagonist pre-treatment, or the protease-activated receptor (PAR)-2 agonists tryptase (0.5–5 nM) and SLIGKV (100 and 400 µM). The cells were then stimulated with interleukin (IL)-1ß and/or tumour necrosis factor (TNF)- (10 ng·mL^–1) or left unstimulated for 24 h. Release of GM-CSF and RANTES was determined by ELISA and prostaglandin (PG)E₂ measured by enzyme immunoassay.

Neither histamine nor tryptase induced ASM GM-CSF or RANTES secretion. However, histamine increased IL-1ß-induced GM-CSF release and markedly reduced TNF--induced RANTES release by both asthmatic and nonasthmatic cells to a similar extent, but did not modulate PGE₂ release. All changes involved activation of the histamine H1 receptor as they were partially or fully blocked by chlorpheniramine, but not ranitidine. Tryptase, via its proteolytic activity, also potentiated GM-CSF, but not RANTES, release from asthmatic and nonasthmatic ASM cells induced by both cytokines. PAR-2 involvement in the tryptase potentiation was unlikely because SLIGKV had no effect.

In conclusion, mast cells, through histamine and tryptase, may locally modulate airway smooth muscle-induced inflammation in asthma.

This article has been cited by other articles:

				P. Bradding Mast cell regulation of airway smooth muscle function in asthma Eur. Respir. J., May 1, 2007; 29(5): 827 - 830. [Full Text] [PDF]