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Evidence of ongoing mast cell and eosinophil degranulation in symptomatic asthma airway
D H Broide1, G J Gleich, A J Cuomo
1Department of Medicine, University of California, San Diego.
Abstract:
To assess whether mast cell and eosinophil (EOS) degranulation occurs in the airway of subjects with moderately symptomatic asthma, we have measured levels of preformed mast cell-derived mediators (histamine and tryptase) and EOS-derived mediators (major basic protein and EOS-derived neurotoxin) in bronchoalveolar lavage fluid (BALF) obtained from patients with symptomatic (N = 14) and asymptomatic asthma (N = 9) and patients without asthma (N = 6). Both the FEV1 (1.52 +/- 0.33 L:55% +/- 15% of predicted FEV1) and the forced expiratory flow at 50% (FEF50) (1.11 +/- 0.62 L/sec:26% +/- 14% of predicted FEF50) in the patients with symptomatic asthma were significantly lower than the corresponding values for FEV1 (3.16 +/- 0.45 L:86% +/- 10% of predicted FEV1) and the FEF50 (4.04 +/- 1.54 L/sec:71% +/- 25% of predicted FEF50) in the patients with asymptomatic asthma. Levels of histamine (4.8 +/- 5.0 ng/ml versus 0.2 +/- 0.2 ng/ml) (p = 0.05), EOS-derived neurotoxin (420.6 +/- 959.4 ng/ml versus 12.6 +/- 7.7 ng/ml) (p = 0.05), major basic protein (31.4 +/- 46.6 ng/ml versus less than 9 ng/ml) (p = 0.05), and percent EOSs (10.6% +/- 7.0% versus 1.1% +/- 0.9% of BAL cells) (p = 0.0006) were all significantly elevated in BALF from symptomatic compared to asymptomatic patients with asthma. The elevated levels of tryptase (13.2 +/- 14.8 ng/ml versus 3.9 +/- 3.9 ng/ml) in BALF from symptomatic compared to asymptomatic patients with asthma approximated, but did not reach, statistical significance. Spontaneous histamine release from BAL mast cells of symptomatic patients with asthma was 46% +/- 5% compared to 5% +/- 2% in asymptomatic patients with asthma. In response to antihuman IgE, histamine release from BAL mast cells recovered from asymptomatic patients with asthma increased to 25% +/- 10%, whereas in BAL mast cells of symptomatic patients with asthma, no anti-IgE potentiation of histamine release occurred. This study suggests that mast cell and EOS degranulation is ongoing in the airway of patients with moderately symptomatic asthma.
Insights
Mast cell and eosinophil degranulation occurs in the airways of symptomatic asthma patients, indicated by elevated mediator levels. This ongoing process contributes to airway inflammation in moderately symptomatic asthma.
Area of Science:
- Immunology
- Pulmonology
- Cell Biology
Background:
- Asthma is characterized by airway inflammation involving mast cells and eosinophils (EOS).
- The extent of mast cell and EOS degranulation in symptomatic asthma is not fully understood.
Purpose of the Study:
- To investigate mast cell and EOS degranulation in the airways of individuals with moderately symptomatic asthma.
- To measure specific mediators released by these cells in bronchoalveolar lavage fluid (BALF).
Main Methods:
- Collected BALF from symptomatic asthma patients (N=14), asymptomatic asthma patients (N=9), and non-asthmatic controls (N=6).
- Measured levels of histamine, tryptase, major basic protein, and EOS-derived neurotoxin in BALF.
- Assessed spontaneous and anti-IgE-induced histamine release from bronchoalveolar lavage mast cells.
Main Results:
- Symptomatic asthma patients exhibited significantly lower FEV1 and FEF50 compared to asymptomatic patients.
- Elevated levels of histamine, EOS-derived neurotoxin, major basic protein, and percentage of EOSs were found in BALF of symptomatic asthma patients.
- Symptomatic patients showed higher spontaneous histamine release from mast cells, with no potentiation by anti-IgE.
Conclusions:
- Mast cell and EOS degranulation are actively occurring in the airways of patients with moderately symptomatic asthma.
- These findings suggest a role for ongoing cellular degranulation in asthma pathogenesis.
- The results highlight differences in mast cell activation between symptomatic and asymptomatic asthma.
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