Exotoxin a stimulates fluid reabsorption from the distal airspaces
of the lung in anesthetized rats.
Pittet, J. F., S. Hashimoto, M. Pian, M. C. McElroy, G. Nitenberg, and
J. P. Wiener-Kronish.
Departments of Anesthesia, Medicine, and Pediatrics, and
Cardiovascular Research Institute, Univ. of California, San
Francisco, CA, 94143
APStracts 2:0171L, 1995.
To determine whether exotoxin A may affect the transport of fluid
across the lung epithelium, two isogenic strains of P. aeruginosa
PA103 (108 cfu), one (PA103 Tox[omega]) with a structural gene
mutation in exotoxin A, were instilled into the distal airspaces of
anesthetized rats. PA103 parental strain but not its mutant,
stimulated the removal of fluid from the distal airspaces of the
lung. Instillation of exotoxin A alone caused a dose-dependent
increase in the fluid transport across the lung epithelium.
Instillation of amiloride (10-3 M) with exotoxin A demonstrated that
this effect depended on increased uptake of sodium across the lung
epithelium. The absence of stimulation after instillation of an
exotoxin A mutant (PE_Glu553) without ADP-ribosyltransferase activity
demonstrated that the effect of exotoxin A depended on its ADP
-ribosyltransferase activity. Finally, the instillation of exotoxin A
in rats depleted of macrophages indicated that the effect of exotoxin
A was not secondary to the activation of alveolar macrophages by this
toxin. In conclusion, these results indicate that the in vivo release
of exotoxin A by live airspace P. aeruginosa directly stimulates the
fluid removal from the airspaces by the lung epithelium. This may
alter the volume or composition of airway secretions, and may
contribute to the lung disease in patients infected with P.
aeruginosa.
Received 7 February 1995; accepted in final form 23 August 1995.
APS Manuscript Number L42-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95