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1 Laboratoire de Recherche en Pathologie Infectieuse, EA 2689, 59045 Lille; Laboratoire de 4 Biophysique and 3 Bactériologie, Hôpital Calmette, Centre Hospitalier Regional Universitaire de Lille, 59037 Lille; 2 Service d'Anatomie et de Cytologie Pathologiques, Faculté Libre de Médecine, Université Catholique de Lille, 59000 Lille, France; 6 Department of Anesthesia and Perioperative Care, University of California, San Francisco, California 94143-0130; and 5 Department of Medicine, Louisiana State University Medical Center, New Orleans, Louisiana 70112
We have previously
reported that keratinocyte growth factor (KGF) attenuates
-naphthylthiourea-induced lung injury by upregulating alveolar fluid
transport. The objective of this study was to determine the effect of
KGF pretreatment in Pseudomonas aeruginosa pneumonia. A 5%
bovine albumin solution with 1 µCi of 125I-labeled human
albumin was instilled into the air spaces 4 or 24 h after
intratracheal instillation of P. aeruginosa, and the concentration of unlabeled and labeled proteins in the distal air
spaces over 1 h was used as an index of net alveolar fluid clearance. Alveolocapillary barrier permeability was evaluated with an
intravascular injection of 1 µCi of 131I-albumin. In
early pneumonia, KGF increased lung liquid clearance (LLC) compared
with that in nonpretreated animals. In late pneumonia, LLC was
significantly reduced in the absence of KGF but increased above the
control value with KGF. KGF pretreatment increased the number of
polymorphonuclear cells recovered in the bronchoalveolar lavage fluid
and decreased bacterial pulmonary translocation. In conclusion, KGF
restores normal alveolar epithelial fluid transport during the acute
phase of P. aeruginosa pneumonia and LLC in early and late
pneumonia. Host response is also improved as shown by the increase in
the alveolar cellular response and the decrease in pulmonary
translocation of bacteria.
pneumonia; lung liquid clearance
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