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Nasal provocation with AMP
  1. MADELEINE ENNIS,
  2. PAUL FORSYTHE
  1. Department of Clinical Biochemistry
  2. Institute of Clinical Science
  3. The Queen’s University of Belfast
  4. Belfast BT12 6BJ, UK
  5. Department of Respiratory Medicine
  6. Belfast City Hospital
  7. Belfast BT9 7AB, UK
    1. LORCAN P A MCGARVEY,
    2. LIAM G HEANEY,
    3. JOSEPH MACMAHON
    1. Department of Clinical Biochemistry
    2. Institute of Clinical Science
    3. The Queen’s University of Belfast
    4. Belfast BT12 6BJ, UK
    5. Department of Respiratory Medicine
    6. Belfast City Hospital
    7. Belfast BT9 7AB, UK
      1. R POLOSA
      1. Istituto di Malattie dell’Apparato Respiratorio
      2. Università degli Studi di Catania
      3. Via Passo Gravina 187
      4. 95125 Catania
      5. Italy

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        We read with interest the article on histamine release following nasal provocation with adenosine 5′-monophosphate (AMP) recently published in Thorax by Polosaet al.1 This is a further in vivo demonstration of the histamine releasing ability of adenosine in the respiratory tract. However, in contrast to the in vitro studies described in the paper where adenosine exerts a modulatory effect on mast cell mediator release, we have demonstrated the direct histamine releasing ability of this molecule on mast cells in the bronchoalveolar lavage (BAL) fluid.2 3 In samples of BAL fluid from 37 of 54 patients attending hospital for routine bronchoscopy, adenosine alone caused histamine release (maximum 20.6 (2.5)% of the total cellular content of the amine). The adenosine receptor agonists R-PIA, NECA, and CGS21680 also induced histamine release from BAL fluid mast cells. Preincubation of BAL fluid mast cells with the adenosine receptor antagonist xanthine amine congener caused significant inhibition of the response to adenosine (p = 0.007).

        Our findings indicate a means by which adenosine challenge of the airways can induce bronchoconstriction and support a role for adenosine in the pathophysiology of asthma. The results suggest that cells obtained from BAL fluid may provide the ideal model for the testing of novel, adenosine receptor, targeted therapies for asthma. The inter-individual variability in response to adenosine and adenosine agonists is therefore most probably due to the variation in the clinical histories of this unpreselected population. Previously we have found a wide variation in response to substance P in such unpreselected patients, although the variation in response was not present in further studies in a clearly defined asthmatic population.4 5 We are currently investigating the action of adenosine on BAL fluid cells employing carefully defined subject groups of atopic asthmatic subjects, atopic non-asthmatic subjects, and non-atopic non-asthmatic controls.

        References

        author’s reply That airway responsiveness to nebulised adenosine is a more selective indicator of allergic inflammation than other non-specific stimuli such as histamine or methacholine is supported by a number of clinical studies.1-1 Although activation of neural pathways1-2 1-3 and the intrinsic hyperresponsiveness of the bronchial smooth muscle to adenosine1-4 may also contribute to adenosine induced bronchoconstriction in asthma, enhanced mast cell releasability in vivo is a primary determinant for these responses.

        We are glad to learn that, in keeping with our previous findings in the lower1-5 and upper airways,1-6 Enniset al have recently shown that adenosine elicits a significant histamine release from BAL fluid mast cells in 37 out of 54 consecutive patients undergoing routine bronchoscopy.1-7 It would be of interest to know whether adenosine potentiates histamine releasability in those BAL fluid mast cells obtained from atopic individuals and to investigate whether PC20 adenosine correlates with the extent of mast cell releasability. This would further substantiate the view of adenosine bronchial provocation as a potential new marker of airway inflammation in asthma.

        Interestingly, Ennis et al provide evidence for an A2A-mediated mechanism for the adenosine induced histamine release from BAL fluid mast cells (since CGS21680 is a selective A2A agonist), whereas A2B receptors are mainly indicated to be involved in the activation of human mast cells.1-8 This needs to be carefully investigated as the appreciation of the potential role of A2A receptors in mediating adenosine induced responses in human mast cells raises the possibility that these receptors could become the target for future drug development.

        References

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