KGF improves alterations of lung permeability and bronchial epithelium in allergic rats

¹ INSERM U774, Institut Pasteur, Université de Lille II, Lille, France
² Laboratoire de Recherche en Pathologie Infectieuse, EA2689, Lille, France
³ Laboratoire de pathologie, U 728 Inserm, Université Paris 7, IUH -IFR 105, Hopital Saint Louis, AP-HP, Paris
⁴ Laboratoire de Biophysique; CHRU de Lille, 59037 Lille, France

^* To whom correspondence should be addressed. E-mail: philippe.gosset{at}pasteur-lille.fr.

	Abstract

Chronic allergic asthma is associated with marked inflammatory reaction, microvascular leakage and epithelium injury. As previously shown in a rat model of chronic asthma, these alterations increased lung permeability and distal airway fluid clearance. Keratinocyte growth factor (KGF) has been shown to induce epithelial cell proliferation and to protect from acute lung injuries. Therefore, we evaluated the potential role of KGF treatment on lung permeability and airway inflammation in rats with chronic asthma.

KGF (1mg·kg^-1) was administered intravenously, before the last ovalbumin (OVA) challenge in sensitized rats. Permeability was assessed by the leak of radiolabeled albumin from the alveolar and the systemic compartments. Histopathologic analysis was also performed.

Treatment with KGF decreased the leak of both markers and the level of extravascular lung water in sensitized rats challenged with OVA. KGF treatment also reduced the inflammatory cell number in bronchoalveolar lavage but not in bronchial mucosa. KGF markedly limited the allergen-induced alterations in epithelium integrity and expression of the intercellular junction proteins: -catenin and ZO-1.

In conclusion, KGF administration markedly limits lung permeability and airway inflammation, an effect associated with a decrease in epithelium alterations during chronic allergic asthma. These data open new prospects in the therapeutic strategy of asthma.

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