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Increased numbers of hypodense alveolar macrophages in patients with bronchial asthma
P Chanez1, J Bousquet, I Couret
1Cliniques des Maladies Respiratoires, Hôpital Gui de Chauliac, Montpellier, France.
Abstract:
Alveolar macrophages (AM) are among the cells involved in the bronchial inflammation of asthma. It has been shown that AM are a heterogeneous cell population in normal subjects. The heterogeneity of AM from 36 asthmatic patients and 23 normal subjects was studied using Percoll density fractionation. AM recovered from asthmatic patients are mainly in the lower density fractions (1.03 and 1.04 g/ml), whereas AM from normal subjects are in the higher density fractions (1.05 and 1.07 g/ml). Electron microscopic studies showed that low density AM of both asthmatic and normal subjects appear to have morphologic characteristics of activated cells by comparison with high density AM that present characteristics of quiescent cells in both asthmatic and normal subjects. The functional activity of AM fractions of asthmatic and control subjects was assessed using the release of the oxygen free radicals induced by opsonized zymosan and TxB2 generation by A23187. There was no difference between the five fractions of asthmatic or control subjects with regard to oxygen species release. The TxB2 generation was increased in the low density AM from asthmatics when compared with the same fractions of normal subjects. The hypodense cells produced less TxB2 than did cells of higher density in both asthmatic and normal subjects. The density of AM was correlated with the recent instability of the asthma but not with the severity of it. This study shows that AM from asthmatic subjects, when compared with those from control subjects, are heterogeneous, hypodense cells and that they predominate. Hypodense AM did not appear to be hyperresponsive in vitro and may have been already committed into the airways.
Insights
Asthma patients have more low-density alveolar macrophages (AM), which show signs of activation. These hypodense AM may be involved in airway inflammation, correlating with asthma instability.
Area of Science:
- Immunology
- Pulmonology
- Cell Biology
Background:
- Alveolar macrophages (AM) are key players in asthma's bronchial inflammation.
- AM exhibit heterogeneity in both healthy individuals and asthmatics.
Purpose of the Study:
- To investigate the heterogeneity of alveolar macrophages in asthma.
- To compare AM density and function between asthmatic and normal subjects.
Main Methods:
- Percoll density fractionation was used to separate AM from 36 asthmatic and 23 normal subjects.
- Electron microscopy assessed cell morphology.
- Functional assays measured oxygen free radical release and thromboxane B2 (TxB2) generation.
Main Results:
- Asthmatic AM predominantly occupied lower density fractions (1.03-1.04 g/ml) compared to normal subjects (1.05-1.07 g/ml).
- Low-density AM in asthmatics showed increased TxB2 generation versus normal subjects.
- AM density correlated with recent asthma instability, not severity.
Conclusions:
- Asthma is characterized by a predominance of heterogeneous, hypodense AM.
- Hypodense AM may be pre-committed to airway involvement rather than being hyperresponsive in vitro.