In this review, we discuss the role of pulmonary surfactant in the host defense against respiratory pathogens, including novel coronavirus SARS-CoV-2. In the lower respiratory system, the virus uses angiotensin-converting enzyme 2 (ACE2) receptor in conjunction with serine protease TMPRSS2, expressed by alveolar type II (ATII) cells as one of the SARS-CoV-2 target cells, to enter. ATII cells are the main source of surfactant. After their infection and the resulting damage, the consequences may be severe and may include injury to the alveolar-capillary barrier, lung edema, inflammation, ineffective gas exchange, impaired lung mechanics and reduced oxygenation, which resembles acute respiratory distress syndrome (ARDS) of other etiology. The aim of this review is to highlight the key role of ATII cells and reduced surfactant in the pathogenesis of the respiratory form of COVID-19 and to emphasize the rational basis for exogenous surfactant therapy in COVID-19 ARDS patients.
In experiments on 51 healthy anaesthetized and paralyzed rabbits the changes in parameters of mechanics of breathing during high frequency jet ventilation (HFJV) were determined and the mechanisms responsible for these changes were investigated. In the first series of experiments with two groups of animals ventilated by HFJV with relative inspiratory time ti = 0.5 and ti = 0.7 airway resistance (Raw) after 5 h of HFJV in the ti = 0.5 group increased from 1.14±0.05 to 2.31±0.09 kPa.l_1.s (P<0.001), in the ti = 0.7 group from 1.22±0.04 to 1.78±0.08 kPa.l-1.s (P<0.01). Dynamic compliance (Cdyn) decreased in the ti = 0.5 group from 0.041 ±0.004 to 0.017±0.001 l.kPa-1 (P<0.01) and in the ti = 0.7 group from 0.034± 0.003 to 0.022± 0.002 l.kPa-1 (P<0.01). In the second series of experiments a group of animals was ventilated by HFJV after cervical vagotomy. The deterioration of Raw and Cdyn was significantly reduced in vagotomized rabbits in comparison to the controls without vagotomy. Finally, the study of phospholipid content in bronchoalveolar lavage fluid revealed no significant differences after 5 h of artificial ventilation or spontaneous breathing. These data indicate that HFJV results in changes in the parameters of mechanics of breathing in healthy lungs, which may be attenuated, but not fully eliminated, by bilateral cervical vagotomy. The decrease in Cdyn and increase in Raw are probably not due to changes in the pulmonary surfactant content.
The respiratory system is constantly exposed to pathogens which enter the lungs by inhalation or via blood stream. Lipopolysaccharide (LPS), also named endotoxin, can reach the airspaces as the major component of the outer membrane of Gram-negative bacteria, and lead to local inflammation and systemic toxicity. LPS affects alveolar type II (ATII) cells an d pulmonary surfactant and although surfactant molecule has the effective protective mechanisms, excessive amount of LPS interacts with surfactant film and leads to its inactivation. From immunological point of view, surfactant specific proteins (SPs) SP-A and SP-D are best characterized, however, there is increasing evidence on the involvement of SP-B and SP-C and certain phospholipids in immune reactions. In animal models, the instillation of LPS to the respiratory system induces acute lung injury (ALI). It is of clinical importance that endotoxin-induced lung injury can be favorably influenced by intratracheal instillation of exogenous surfactant. The beneficial effect of this treatment was confirmed for both natural porcine and synthetic surfactants. It is believed that the surfactant preparations have anti-inflammatory properties through regulating cytokine production by inflammatory cells. The mechanism by which LPS interferes with ATII cells and surfactant layer, and its consequences are discussed below., M. Kolomaznik, Z. Nova, A. Calkovska., and Obsahuje bibliografii