Changes in phenotype and phenotypic flexibility of alveolar macrophages in inflammatory pulmonary diseases

Summary. We studied phenotypic specificity and flexibility of innate immunity cells, such as alveolar macrophages isolated from bronchoalveolar lavage fluid (BALF) in patients with chronic obstructive pulmonary disease (COPD), bronchial asthma (BA) and sarcoidosis which are lung diseases with inflammatory component. We found that M1 macrophages prevailed in COPD and sarcoidosis patients and M2 macrophages prevailed in BA patients though the macrophage populations were not monophenotypic. The investigation of macrophage phenotypic flexibility in COPD, BA and sarcoidosis demonstrated that different phenotypic markers show different macrophage phenotypic flexibility in COPD, BA and sarcoidosis. This fact allows suggestion that phenotypic flexibility is specific to a certain parameter (receptor, structural or functional flexibility). The obtained data extend our knowledge on pathogenesis of pulmonary diseases and can be used to develop a new approach for management of these diseases.

1. Министерство здравоохранения и социального развития Российской Федерации, Департамент развития медицинской помощи и курортного дела ФГУ "Центральный научно-исследовательский институт организации и информатизации здравоохранения" Росздрава. Статистические материалы, 2009. www.mednet.ru

2. Малышев И.Ю., Лямина С.В., Шимшелашвили Ш.Л., Вассерман Е.Н. Функциональные ответы альвеолярных макрофагов, сурфактантный белок D и заболевания легких. Пульмонология 2011; 3: 101–107.

3. Лямина С.В., Круглов С.В., Веденикин Т.Ю., Малышев И.Ю. Новая стратегия управления иммунным ответом при заболеваниях легких – роль сурфактантного белка D как бивалентного фактора репрограммирования макрофагов. Фундамент. исслед. 2011; 1: 90–98.

4. Martinez F.O., Sica A., Mantovani A., Locati M. Macrophage activation and polarization. Front Biosci 2008; 1 (13): 453–461.

5. Löfdahl J.M., Wahlström J., Sköld C.M. Different inflammatory cell pattern and macrophage phenotype in chronic obstructive pulmonary disease patients, smokers and nonsmokers. Clin. Exp. Immunol. 2006; 145 (3): 428–437.

6. Pons A.R., Noguera A., Blanquer D. et al. Phenotypic characterisation of alveolar macrophages and peripheral blood monocytes in COPD. Eur. Respir. J. 2005; 25 (4): 647–652.

7. Woodruff P.G., Modrek B., Choy D.F. et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am. J. Respir. Crit. Care Med 2009; 180 (5): 38–395.

8. Mills C.D., Kincaid К., Alt J.M. et al. M-1/M-2 macrophages and the Th1/Th2 paradigm. J. Immunol. 2000; 164: 6166–6173.

9. Лямина С.В., Круглов С.В., Веденикин Т.Ю. и др. Альтернативное репрограммирование М1/М2 фенотипа перитонеальных макрофагов мышей in vitro с помощью интерферона гамма и интерлейкина 4. Клеточ. технол. в биол. и мед. 2011; 4: 235.

10. Thum T., Erpenbeck V.J., Moeller J. et al. Expression of xenobiotic metabolizing enzymes in different lung compartments of smokers and non-smokers. Environ. Hlth Perspect. 2006; 114 (11): 1655–1661.

11. Orosi Р., Nugent К. Studies of phagocytic and killing activities of alveolar macrophages in patients with sarcoidosis. Lung 1993; 171 (4): 225–233.

12. Gardai S.J., Xiao Y.4Q., Dickinson M. et al. By binding SIRP-alpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation. Cell 2003; 115: 13–23.

13. Drent M., Mulder P.G.H., Wagenaar S.S. et al. Differences in BAL fluid variables in interstitial lung diseases evaluated by discriminant analysis. Eur. Respir. J. 1993; 6: 803–810.

14. Грачев А.Н. Гетерогенность и функциональная пластичность макрофагов второго типа активации: Автореф. дис. … д-ра мед. наук. М.; 2008.

15. Ikezumi Y., Suzuki T., Karasawa T. et al. Contrasting effects of steroids and mizoribine on macrophage activation and glomerular lesions in Rat Thy-1 mesangial proliferative glomerulonephritis. Am. J. Nephrol. 2010; 31: 273–282.