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Published on: July 10, 2014
Alveolar macrophage phagocytosis is impaired in children with poorly controlled asthma
Anne M Fitzpatrick1, Fernando Holguin, W Gerald Teague
1Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA. anne.fitzpatrick@emory.edu
Background:
Lower respiratory tract infection is a differentiating feature of children with poorly controlled asthma.
Objective:
Given the role of alveolar macrophages (AMs) in innate immunity, we hypothesized that AM phagocytosis might be impaired in poorly controlled asthma.
Methods:
Bronchoalveolar lavage fluid AMs were isolated from 28 asthmatic children (moderate asthma, n = 12; severe asthma, n = 16), 10 nonasthmatic children with chronic cough treated with inhaled corticosteroids, and 10 healthy adult control subjects. AMs were stimulated with LPS and exposed to fluorescein isothiocyanate-conjugated Staphylococcus aureus for 2 hours. Phagocytosis was quantified by using a phagocytic index (PI) calculated from the percentage of phagocytic cells multiplied by the relative fluorescence (RFU) units of S. aureus per cell. Apoptosis was determined from the percentage of cells positive for poly (adenosine diphosphate-ribose) polymerase.
Results:
Phagocytosis as measured by using the unstimulated PI was decreased in subjects with poorly controlled asthma (healthy control subjects, 9330 +/- 3992 RFU; chronic cough, 9042 +/- 5976 RFU; moderate asthma, 4361 +/- 2536 RFU; severe asthma, 3153 +/- 1886 RFU; P < .001) and remained unchanged with LPS stimulation. Children with severe asthma also had increased AM apoptosis, both the unstimulated and LPS-simulated states (P < .001), which correlated with the PI.
Conclusions:
AM function is compromised in children with poorly controlled asthma and is characterized by decreased phagocytosis and increased apoptosis.
Insights
Alveolar macrophage phagocytosis is impaired in children with poorly controlled asthma, showing decreased function and increased apoptosis. This compromise in immune cell activity may contribute to respiratory infections in pediatric asthma patients.
Area of Science:
- Immunology
- Pulmonology
- Pediatrics
Background:
- Lower respiratory tract infections are common in children with poorly controlled asthma.
- Alveolar macrophages (AMs) play a crucial role in innate immunity.
- Impaired AM phagocytosis was hypothesized in poorly controlled asthma.
Purpose of the Study:
- To investigate the phagocytic capacity and apoptosis rates of alveolar macrophages in children with moderate and severe asthma.
- To compare AM function between asthmatic children, children with chronic cough, and healthy adults.
Main Methods:
- Alveolar macrophages were isolated from bronchoalveolar lavage fluid of asthmatic children, children with chronic cough, and healthy adults.
- AMs were stimulated with LPS and exposed to Staphylococcus aureus to quantify phagocytosis via a phagocytic index (PI).
- Apoptosis was measured by the percentage of cells positive for poly (adenosine diphosphate-ribose) polymerase.
Main Results:
- Unstimulated phagocytic index (PI) was significantly decreased in children with moderate and severe asthma compared to controls.
- LPS stimulation did not alter phagocytosis levels in asthmatic children.
- Children with severe asthma exhibited increased AM apoptosis, which correlated with reduced PI.
Conclusions:
- Alveolar macrophage function is compromised in children with poorly controlled asthma.
- Decreased phagocytosis and increased apoptosis characterize AMs in pediatric asthma.
- These functional deficits in AMs may underlie increased susceptibility to respiratory infections in asthmatic children.
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