EFFECT OF ENDOCYTOSIS INHIBITORS ON ALVEOLAR CLEARANCE OF ALBUMIN, IMMUNOGLOBULIN-G, AND SP-A IN RABBITS

Protein in the alveolar space may be cleared by endocytosis and degrad ation inside alveolar epithelial cells, by transcytosis across the alv eolar epithelium, or by restricted diffusion through the epithelium. T he relative contributions of these three pathways to clearance of larg e quantities of protein from the air spaces is not known. This study i nvestigated the effects of monensin and nocodazole, agents which inhib it endocytosis in cell culture, on alveolar epithelial protein transpo rt in anesthetized rabbits. There was evidence that monensin and nocod azole inhibited endocytosis by the alveolar epithelium in vivo. Nocoda zole increased the number of vesicles in the alveolar epithelium and c apillary endothelium. Monensin increased vesicle density in the endoth elium. These results suggested that the inhibitors disrupted microtubu les or interrupted cellular membrane traffic in the lung. Both inhibit ors decreased lung parenchymal uptake of immunoreactive human albumin from the air spaces. Monensin and nocodazole inhibited albumin uptake in cultured alveolar type II cells. Monensin increased the amount of I -125-labeled surfactant protein A associated with the lungs, compared with the quantity remaining in the air space 2 h after instillation. A lthough the drugs decreased alveolar epithelial protein uptake, they d id not decrease alveolar clearance of I-125-labeled immunoglobulin G o r I-131-labeled albumin in anesthetized rabbits. Thus monensin- and no codazole-sensitive protein-uptake pathways do not account for most alv eolar protein clearance when the distal air spaces are filled with a p rotein solution.