title: A novel lung injury animal model using KL-6-measurable human MUC1-expressing mice.
abstract: KL-6, an epitope of MUC1 mucin expressed on type II pneumocytes and bronchiolar epithelia in humans, is a sensitive serum marker for interstitial pneumonia. However, an in vivo model for KL-6 has not been established because no KL-6 epitope is expressed in animals other than humans and apes. To investigate whether KL-6 is detectable in human MUC1-expressing (hMUC1-exp) mice and whether KL-6 level reflects the degree of lung injury, we examined serum and bronchoalveolar lavage fluid (BALF) levels of KL-6 and surfactant protein-D (SP-D) in either lipopolysaccharide (LPS)- or bleomycin (BLM)-induced lung injury models. KL-6 was expressed on type II pneumocytes and bronchiolar epithelial cells in naïve hMUC1-exp mice. Serum KL-6 levels in these mice were comparable to those in humans, and KL-6 levels in BALF were significantly higher than those in sera. In the LPS model, KL-6 levels in sera and BALF were slightly increased, although SP-D levels were markedly increased. During the inflammatory phase in the BLM model, KL-6 levels in sera were greatly increased, but those in BALF were decreased. Serum KL-6 levels were positively correlated with BALF albumin levels, a representative marker for increased the alveolar-capillary permeability. SP-D levels in sera and BALF were significantly increased compared to the corresponding levels in the LPS model. The increase in serum KL-6 levels appeared to be associated with the disruption of alveolar-capillary barrier after BLM-induced lung injury. This hMUC1-exp mouse can be used for assessment of KL-6 in vivo during lung injury.
authors: Department of Hematology and Respiratory Medicine, Kochi University, Nankoku City, Kochi 783-8505, Japan. msakai@kochi-u.ac.jp
authors: Mizu
authors: M
authors: Sakai
authors: Tetsuya
authors: T
authors: Kubota
authors: Hiroshi
authors: H
authors: Ohnishi
authors: Akihito
authors: A
authors: Yokoyama
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000097:blood / Q000378:metabolism; D001761:Bleomycin / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D006801:Humans; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D018396:Mucin-1 / Q000032:analysis / Q000097:blood / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D008070:Lipopolysaccharides; C060192:MUC1 protein, human; D018396:Mucin-1; D001761:Bleomycin