title: Partial SP-B deficiency perturbs lung function and causes air space abnormalities.
abstract: Surfactant protein B (SP-B) is required for function of newborn and adult lung, and partial deficiency has been associated with susceptibility to lung injury. In the present study, transgenic mice were produced in which expression of SP-B in type II epithelial cells was conditionally regulated. Concentrations of SP-B were maintained at 60-70% of that normally present in control. Immunostaining for SP-B demonstrated cellular heterogeneity in expression of the protein. In subsets of type II cells in which SP-B staining was decreased, immunostaining for pro-SP-C was increased and lamellar body ultrastructure was disrupted, consistent with focal SP-B deficiency. Fluorescence-activated cell sorting analyses of freshly isolated type II cells identified a population of cells with low SP-B content and a smaller population with increased SP-B content, confirming nonuniform expression of the SP-B transgene. Focal air space enlargement, without cellular infiltration or inflammation, was observed. Pressure-volume curves indicated that maximal tidal volume was unchanged; however, hysteresis was modestly altered and residual volumes were significantly decreased in the SP-B-deficient mice. Chronic, nonuniform SP-B deficiency perturbed pulmonary function and caused air space enlargement.
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Neonatology, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA.
authors.forename: Lori L
authors.initials: LL
authors.lastname: Nesslein
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Melton
authors.forename: Machiko
authors.initials: M
authors.lastname: Ikegami
authors.forename: Cheng-Lun
authors.initials: CL
authors.lastname: Na
authors.forename: Susan E
authors.initials: SE
authors.lastname: Wert
authors.forename: Ward R
authors.initials: WR
authors.lastname: Rice
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Whitsett
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Weaver
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D008168:Lung / Q000033:anatomy & histology / Q000502:physiology*; D008170:Lung Compliance; D008176:Lung Volume Measurements; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D037701:Pulmonary Surfactant-Associated Protein B / Q000172:deficiency* / Q000235:genetics*; D015656:Respiratory Mechanics
chemical_list: D037701:Pulmonary Surfactant-Associated Protein B