Alveolar macrophage phagocytosis is impaired in children with poorly controlled asthma

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Abstract

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–conjugatedStaphylococcus aureusfor 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 ofS aureusper 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.

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