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Surfactant modifies the lymphoproliferative activity of macrophages in hypersensitivity pneumonitis
1Unité de Recherche, Centre de Pneumologie, Hôpital and Université Laval, Ste.-Foy, Québec, Canada.
Abstract:
Alveolar macrophages (AM) from normal individuals suppress mitogen-induced peripheral blood mononuclear cell (PBMC) proliferation, whereas cells from patients with hypersensitivity pneumonitis (HP) enhance PBMC. Because surfactant components can interfere with AM functions, we tested the effect of Survanta (a modified bovine surfactant) and surfactant fractions isolated from bronchoalveolar lavage of normal subjects and HP patients on AM-induced lymphoproliferation. Surfactant fractions were isolated from bronchoalveolar lavage fluids by differential centrifugation into total aggregates (TA) and large aggregates (LA). Surfactant preparations (200 micrograms/ml) from 10 normal subjects (N) or 12 HP patients or of Survanta were added to AM-PBMC cocultures stimulated with phytohemagglutinin (PHA) at 1:1 and 2:1 ratios. Results, expressed as percent of PHA-induced PBMC proliferation cocultures without surfactant, show that normal surfactant and Survanta decrease mitogen-induced proliferation of cells to a larger extent than surfactant from HP patients. For AM-to-PBMC ratios of 1:1, the results were as follows: N TA 10.58 +/- 2.75% (mean +/- SE), N LA 12.96 +/- 2.78%, HP TA 43.09 +/- 7.81%, HP LA 61.64 +/- 7.77%, and Survanta 16.70 +/- 2.95%. Similar data were obtained in 2:1 cocultures. Because surfactant components interact with AM, alterations of surfactant composition in lymphocytic diseases, mainly in the LA fraction, may account for the lack of suppressive activity in AM of HP patients and the observed alveolitis.
Insights
Surfactant from hypersensitivity pneumonitis (HP) patients impairs alveolar macrophage (AM) function, unlike normal surfactant or Survanta. This altered surfactant may explain HP-related alveolitis by reducing AM
Area of Science:
- Immunology
- Pulmonary Medicine
- Cell Biology
Background:
- Alveolar macrophages (AM) normally suppress peripheral blood mononuclear cell (PBMC) proliferation.
- In contrast, AM from hypersensitivity pneumonitis (HP) patients enhance PBMC proliferation.
- Surfactant components are known to influence AM function.
Purpose of the Study:
- To investigate the effect of modified bovine surfactant (Survanta) and native surfactant fractions on AM-induced lymphoproliferation.
- To determine if altered surfactant composition in HP patients contributes to their immune dysregulation.
Main Methods:
- Surfactant fractions (total aggregates - TA, large aggregates - LA) were isolated from bronchoalveolar lavage fluids of normal subjects and HP patients.
- Surfactant preparations and Survanta were added to AM-PBMC co-cultures stimulated with phytohemagglutinin (PHA).
- Lymphoproliferation was measured at different AM-to-PBMC ratios (1:1 and 2:1) and expressed as a percentage of PHA-induced proliferation without surfactant.
Main Results:
- Normal surfactant and Survanta significantly decreased PHA-induced PBMC proliferation compared to HP surfactant.
- Surfactant from HP patients showed markedly less suppression of PBMC proliferation (HP TA: 43.09%, HP LA: 61.64% at 1:1 ratio) than normal surfactant (N TA: 10.58%, N LA: 12.96%).
- Survanta demonstrated significant suppressive activity (16.70% at 1:1 ratio).
Conclusions:
- Alterations in surfactant composition, particularly in the large aggregate fraction, may be responsible for the diminished suppressive activity of AM in HP patients.
- These surfactant-mediated changes in AM function could contribute to the pathogenesis of alveolitis in HP.
- Survanta exhibits properties similar to normal surfactant in modulating AM function.
