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Release of mast-cell-derived mediators after endobronchial adenosine challenge in asthma
Abstract:
Preformed and newly generated mediators released from airway mast cells may play a role in adenosine-induced bronchoconstriction. To investigate the possible role of mast-cell-derived mediator release in mediating bronchoconstriction induced by adenosine 5'-monophosphate (AMP), we have examined the fluid obtained by bronchoalveolar lavage for inflammatory mediators and markers of airway permeability immediately after instillation of AMP directly into an airway segment of 10 asthmatic subjects. Eight subjects completed the protocol. When compared with the saline-challenged segment, the response to endobronchial stimulation with AMP was characterized by a prompt reduction in airway caliber paralleled by a significant rise in PGD2, histamine, and tryptase levels in the lavage fluid. After AMP challenge, the median (range) concentration for PGD2 increased from 36 to 205 pg/ml (p = 0.006), for histamine from 184 to 433 pg/ml (p = 0.018), and for tryptase from 0.30 to 0.54 ng/ml (p = 0.013). In addition, a small but significant rise in albumin levels (from 27.8 to 36.1 micrograms/ml; p = 0.031) was detected after endobronchial challenge with AMP. These findings indicate that adenosine-induced responses may be initiated by the acute release of mast-cell-derived mediators, including PGD2, histamine, and tryptase.
Insights
Adenosine monophosphate (AMP) triggers asthma symptoms by causing airway mast cells to release inflammatory mediators. This study found AMP induced significant increases in PGD2, histamine, and tryptase, confirming mast cell involvement in adenosine-induced bronchoconstriction.
Area of Science:
- Pulmonary Medicine
- Allergy and Immunology
- Respiratory Physiology
Background:
- Airway mast cells are implicated in bronchoconstriction.
- Adenosine monophosphate (AMP) can induce airway narrowing.
Purpose of the Study:
- To investigate the role of mast cell mediators in adenosine-induced bronchoconstriction.
- To examine inflammatory mediator release and airway permeability following AMP challenge in asthmatic subjects.
Main Methods:
- Bronchoalveolar lavage fluid was collected after endobronchial instillation of AMP in asthmatic subjects.
- Lavage fluid was analyzed for prostaglandin D2 (PGD2), histamine, tryptase, and albumin levels.
- Airway caliber changes were assessed following AMP challenge.
Main Results:
- AMP challenge led to a significant reduction in airway caliber.
- Concentrations of PGD2, histamine, and tryptase in lavage fluid significantly increased post-AMP challenge.
- A significant rise in albumin levels indicated increased airway permeability.
Conclusions:
- Adenosine-induced bronchoconstriction is mediated by the acute release of mast cell mediators.
- PGD2, histamine, and tryptase are key mediators involved in AMP-induced airway responses in asthma.