Keratinocyte growth factor protects against Pseudomonas aeruginosa-induced lung injury.
We have previously reported that keratinocyte growth factor (KGF) attenuates alpha-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 microCi of (125)I-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 microCi of (131)I-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.
Viget
N B
NB
Laboratoire de Recherche en Pathologie Infectieuse, EA 2689, 59045 Lille, France.
Guery
B P
BP
Ader
F
F
Nevière
R
R
Alfandari
S
S
Creuzy
C
C
Roussel-Delvallez
M
M
Foucher
C
C
Mason
C M
CM
Beaucaire
G
G
Pittet
J F
JF
D000418:Albumins / Q000493:pharmacokinetics; D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D016676:Macrophages, Alveolar / Q000276:immunology / Q000382:microbiology; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011550:Pseudomonas aeruginosa; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D015996:Survival Rate
D000418:Albumins; C496455:Fgf7 protein, rat; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D007457:Iodine Radioisotopes; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors