The Activity of the Transporter Protein P-gp in Human Macrophages Enhances the Effect of Pulmonary Surfactant As an Activator of Phagocytosis

Tarasova, E.K.; Lepekha, L.N.; Masyutin, A.G.; Scherbakova, E.A.; Erokhina, M.V.

Авторы: Tarasova E.K., Lepekha L.N., Masyutin A.G., Scherbakova E.A., Erokhina M.V.
Журнал: Moscow University Biological Sciences Bulletin
Том: 80
Номер: 3
Год издания: 2025
Издательство: Allerton Press
Местоположение издательства: New York, N.Y., United States
Первая страница: 129
Последняя страница: 135
DOI: 10.3103/s0096392525601236
Аннотация: Pulmonary surfactant is an essential component of the respiratory system for the implementation of phagocytosis by alveolar macrophages. Pulmonary tuberculosis is associated with reduced pulmonary surfactant production and impaired phagocytic function of macrophages. The transporter protein P-gp (encoded by ABCB1 gene) is overexpressed in lung cells and exports numerous substrates. The incorporation of P-gp into the plasma membrane alters its characteristics. The aim of this study was to analyze the relationship between P‑gp and the phagocytic activity of macrophages under the influence of exogenous pulmonary surfactant. The study employed scanning electron microscopy and confocal laser scanning microscopy methods, as well as two models of cultured human cells: (1) proinflammatory THP-1 macrophages (P-gp+) infected with M. bovis BCG (this model, when exposed to surfactant, is considered a model of alveolar-like macrophages); and (2) parental myeloblastic leukemia K562 cells (P-gp–) and K562/i-S9 cells (P-gp+) transfected with the ABCB1 gene and induced to adhere. In model 1, it was found that the addition of 1 mg/mL of exogenous pulmonary surfactant for 1 h led to the formation of numerous long filopodia, ruffles, and phagocytic cups as well as a 1.7-fold increase in the phagocytic index. This demonstrates that the surfactant is an effective activator of phagocytosis in infected macrophages. In model 2, it was shown that cell surface activation increased significantly in the presence of P-gp under the influence of exogenous pulmonary surfactant compared to cells without P-gp. It is hypothesized that, due to the interaction between P-gp, ERM complex proteins (ezrin, radixin, moesin) and actin filaments, P-gp+ cells are more potentiated for cell surface activation and phagocytosis than P-gp– cells. Further analysis of the features of infected macrophages’ phagocytosis depending on P-gp activity may contribute to the development of new drugs aimed at regulating the phagocytic activity of macrophages.
Добавил в систему: Масютин Александр Георгиевич

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The Activity of the Transporter Protein P-gp in Human Macrophages Enhances the Effect of Pulmonary Surfactant As an Activator of Phagocytosisстатья

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