Acid aspiration leads to pulmonary endothelial and epithelial cell (EC/
EpC) injury characterized by increased permeability and polymorphonuclear (PMN) leukocyte diapedesis. Actin in the EC/
EpC cytoskeleton has been shown to play a significant role in maintenance of the microvascular junction barrier. This study tests indirectly whether the development of permeability and diapedesis following
acid aspiration is via disruption of the pulmonary cytoskeleton. Manipulation was achieved by the actin microfilament assembler
phalloidin. Anesthetized rats (n = 88) underwent segmental lung installation of 0.1 ml saline or
phalloidin (2 x 10(-6) M). Twenty minutes later 0.1 N HCl, saline, or
phalloidin was introduced. After 3 h there was an increase in wet-to-dry weight (W/D) ratio of 6.6 and 5.1 in the HCl-injected and noninjected sides,
protein concentration, 3,970 and 2,530 micrograms/ml, and accumulation of 93 PMN/ml (x 10(4] in bronchoalveolar lavage (BAL) of the HCl-injected lung. These values were higher than control animals. Local pretreatment with
phalloidin attenuated
acid-induced localized but not generalized permeability with reduction in W/D ratio, BAL
protein concentration, and diapedesis (P less than 0.05).
Acid injection into airways also led to elevated
thromboxane B2 and
leukotriene B4 levels in plasma and BAL (P less than 0.05) and generalized lung leukosequestration, events not affected by
phalloidin. Taken together, these data suggest that
acid aspiration
lung injury is determined largely by loss of integrity of the pulmonary EC/
EpC cytoskeleton with resultant loss of barrier function.