Ventilation and secretion of pulmonary surfactant

Summary Various factors are involved in the regulation of surfactant secretion: chemical agonist; local environmental factors such as mediators, locally produced hormones, and possibly pH; and finally, mechanical stress occurring during lung inflation. Here we suggest a model of regulation which is grouped into three levels: a basal autoregulatory mechanism with local factors being superimposed and a systemic level acting through hormones reaching the lung via the bloodstream. Depending on the situation, the different levels may vary in their importance. For the normal situation, in the absence of stress factors, we suggest the autoregulation of stretch-induced secretion and SP-A inhibition as indicated by in vitro experiments to be the prominent regulatory mechanism for surfactant secretion. From this model, mechanisms can be derived which indicate involvement of the surfactant system in, for example, obstructive lung disease. Support from the literature for this hypothesis is reviewed. Because quantitative measurement of the amount of surfactant-associated phospholipids cannot be done adequately at this time, we suggest testing the relatively risk-free application of exogenous surfactant in a pilot phase based on indications for its involvement and usefulness derived from animal and in vitro experiments.Abbreviations [Ca⁺⁺]_i intracellular free calcium - ARDS adult respiratory distress syndrome - ATP adenosine triphosphate - BAL bronchoalveolar lavage - cAMP cyclic adenosine monophosphate - COPD chronic obstructive pulmonary disease - DAG diacylglycerol - DPPC di-palmitoyl-phosphatidylcholine - EDRF endothelium-derived relaxing factor - IP₃ inositoltriphosphate - IRDS infant respiratory distress syndrome - LT D₄ leukotriene D₄ - LT E₄ leukotriene E₄ - LTC₄ leukotriene C₄ - PC phosphatidylcholine - PEEP positive end expiratory pressure - PIP₂ phosphatidylinositol diphosphate - PMN polymorphonuclear (leukocyte) - SP-A surfactant protein A - SP-B surfactant protein B - SP-C surfactant protein C - SP-D surfactant protein D - TPA 12-O-tetradecanoyl-phorbol-13-acetate