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Alveolar macrophage surface carbohydrate expression is altered in interstitial lung disease as determined by
K C Meyer1, C Powers, N Rosenthal
1Department of Medicine, University of Wisconsin Medical School, Madison.
Insights
Interstitial lung disease alters cell surface glycoconjugates on alveolar macrophages (AM). Lectin binding changes suggest potential influx of immature monocytes or a proinflammatory macrophage phenotype in patients.
Area of Science:
- Immunology
- Cell Biology
- Pulmonology
Background:
- Cell-surface glycoconjugates are crucial for cellular functions like antigen presentation and adhesion.
- These functions can be altered in patients with interstitial lung disease (ILD).
- Lectin binding to cell-surface carbohydrates offers a method to study these alterations.
Purpose of the Study:
- Establish baseline lectin-binding data for bronchoalveolar-lavage-derived cells from normal volunteers.
- Compare lectin-binding properties of cells from normal subjects with those from patients with ILD.
- Investigate alterations in cell-surface glycoconjugate expression in ILD.
Main Methods:
- Collected bronchoalveolar lavage cells from normal volunteers and patients with ILD (idiopathic pulmonary fibrosis, sarcoidosis, amiodarone-induced lung disease).
- Utilized a panel of 21 fluorochrome-coupled plant lectins.
- Employed flow cytometry to analyze lectin binding to alveolar macrophages (AM).
Main Results:
- AM lectin-binding profiles were reproducible in normal subjects.
- AM from ILD patients showed increased binding for specific lectins (PNA, UEA-I, BSL-I, VVL, SJA) compared to normal subjects.
- Increased binding was most pronounced in patients with idiopathic pulmonary fibrosis, suggesting potential monocyte influx or macrophage activation.
Conclusions:
- Demonstrated heterogeneous expression of surface carbohydrate residues on AM and blood monocytes in normal subjects.
- Showed significant alterations in lectin receptor expression on AM from ILD patients.
- Lectin-binding properties may aid in evaluating mononuclear phagocyte populations in ILD, identifying functional subsets and activation states.
Abstract:
Cell-surface-associated glycoconjugates play important roles in cellular functions such as antigen presentation and cell adhesion, functions that may be modulated in patients with interstitial lung disease. Because carbohydrate residues can be recognized by specific lectins, we designed our study to establish baseline data for bronchoalveolar-lavage-derived cells from normal volunteers and to compare the lectin-binding properties of these cells with cells recovered from patients presenting with interstitial lung disease. Cells were obtained from patients with idiopathic pulmonary fibrosis (n = 10), patients with sarcoidosis (n = 20), and patients receiving amiodarone without evidence of clinical lung disease (n = 10) as well as from normal volunteers (n = 8). To determine the pattern of cell-surface glycoconjugate expression on alveolar macrophages (AM), we used a panel of 21 fluorochrome-coupled plant lectins and employed flow cytometry to determine their binding to AM. The labeling profiles of AM were found to be highly reproducible for normal subjects. At the lectin concentrations used for this study, some lectins showed very little binding to AM and some displayed intermediate binding, but the majority of the lectins labeled nearly all AM in samples. Fluorescence intensity varied characteristically for cells labeled with different lectins, providing further refinement and permitting discrimination beyond that provided by data restricted to percent of labeling. AM from patients with interstitial lung disease showed increased binding for the plant-derived lectins PNA, UEA-I, BSL-I, VVL, and SJA compared with AM from normal subjects, being most augmented for AM from patients with idiopathic pulmonary fibrosis. Because peripheral blood monocytes from normal subjects show a higher percentage of labeling with PNA, UEA-I, SJA, and BSL-I than did AM, the increased expression of binding sites for these four lectins by AM from patients with interstitial lung disease may reflect the influx of immature blood monocytes and/or the emergence of a proinflammatory macrophage phenotype. This study demonstrated heterogeneous expression of surface carbohydrate residues by AM and blood monocytes from normal subjects and alterations in carbohydrate receptor expression in interstitial lung disease. Lectin-binding properties may prove useful, therefore, in the evaluation of mononuclear phagocyte populations in interstitial lung disease, especially by the identification of functional subsets and/or changed activation states.