Alveolar-Capillary Membrane-Related Pulmonary Cells as a Target in Endotoxin-Induced Acute Lung Injury

Abstract

The main function of the lungs is oxygen transport from the atmosphere into the blood circulation, while it is necessary to keep the pulmonary tissue relatively free of pathogens. This is a difficult task because the respiratory system is constantly exposed to harmful substances entering the lungs by inhalation or via the blood stream. Individual types of lung cells are equipped with the mechanisms that maintain pulmonary homeostasis. Because of the clinical significance of acute respiratory distress syndrome (ARDS) the article refers to the physiological role of alveolar epithelial cells type I and II, endothelial cells, alveolar macrophages, and fibroblasts. However, all these cells can be damaged by lipopolysaccharide (LPS) which can reach the airspaces as the major component of the outer membrane of Gram-negative bacteria, and lead to local and systemic inflammation and toxicity. We also highlight a negative effect of LPS on lung cells related to alveolar-capillary barrier and their response to LPS exposure. Additionally, we describe the molecular mechanism of LPS signal transduction pathway in lung cells.

Keywords: acute respiratory distress syndrome; alveolar epithelial cells; alveolar macrophages; bacterial lipopolysaccharide; endothelial cells; fibroblasts.

Figure 1

Schematic arrangement of alveolar-capillary membrane-related pulmonary cells. ATI cell—alveolar epithelial type I cell, ATII cell—alveolar epithelial type II cell.

Figure 2

General mechanism of host immune response to Lipopolysaccharide (LPS) through TLR4 signaling. IFN-β—interferon β, IL—interleukin, IRF3—interferon regulatory factor 3, LBP—LPS binding molecule, LPS—lipopolysaccharide, Mal—MyD88 adaptor-like protein, MD2—myeloid differentiation protein 2, MyD88—myeloid differentiation factor 88, TIR domain—Toll/IL-1R homology domain, TLR4—toll-like receptor 4, TNF-α—tumor necrosis factor α, TRAM—TRIF-related adaptor molecule, TRIF—TIR-domain-containing adaptor protein.