Attenuation of acid aspiration edema with phalloidin.
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.
Goldman
G
G
Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
Welbourn
R
R
Klausner
J M
JM
Alexander
S
S
Kobzik
L
L
Valeri
C R
CR
Shepro
D
D
Hechtman
H B
HB
D000280:Administration, Inhalation; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D015777:Eicosanoids / Q000378:metabolism; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000633:toxicity*; D001239:Inhalation; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010590:Phalloidine / Q000494:pharmacology / Q000627:therapeutic use*; D011654:Pulmonary Edema / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains
D015777:Eicosanoids; D010590:Phalloidine; D006851:Hydrochloric Acid