Published ahead of print on February 5, 2003, doi:10.1164/rccm.200112-132OC Am. J. Respir. Crit. Care Med., Volume 167, Number 9, May 2003, 1264-1270 A more recent version of this article appeared on May 1, 2003
Submitted on December 16, 2001 Surfactant homeostasis is maintained in vivo during KGF-induced rat lung type II cell hyperplasiaAntonia Fehrenbach1,1 Center of Anatomy, Division of Electron Microscopy, University of Gottingen, Gottingen, Germany; Department of Internal Medicine (Respiratory Medicine), Clinical Research Group 'Chronic Airway Diseases', Philipps-University, Marburg, Germany, 2 Center of Anatomy, Division of Electron Microscopy, University of Gottingen, Gottingen, Germany, 3 Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany; Department of Respiratory Medicine, Medical School of Hannover, Hannover, Germany, 4 University Children's Hospital Charite, Humboldt-University, Clinic of Neonatology, Berlin, Germany, 5 Department of Functional and Applied Anatomy, Medical School of Hannover, Hannover, Germany, 6 Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany, 7 Department of Internal Medicine (Respiratory Medicine), Clinical Research Group 'Chronic Airway Diseases', Philipps-University, Marburg, Germany * To whom correspondence should be addressed. E-mail: heinz.fehrenbach{at}mailer.uni-marburg.de.
Keratinocyte growth factor (KGF) induces transient proliferation of alveolar type II cells (AEII) associated with surfactant alterations. To test the hypothesis that homeostasis of intracellular phospholipid stores is maintained under KGF induced hyperplasia, we 1) collected tissue from adult rat lungs, fixed for light and electron microscopy 3 days after intratracheal instillation of 5 mg recombinant human (rHu) KGF/kg b.w. or PBS, and from untreated controls (5 animals/group) for design-based stereology of AEII and lamellar body (LB) ultrastructure. 2) We analyzed uptake and distribution of instilled radiolabeled phospholipids. After rHuKGF, AEII-coverage of alveolar walls (PBS:8.3±3.0%; rHuKGF:30.6±4.8%) and number of AEII/ml lung volume (PBS:28.5±6.5x106; rHuKGF:48.2±5.8x106) were increased (p<0.008). Number (PBS:97±25; rHuKGF:54±7) and volume (PBS:45.3±13.8µm3; rHuKGF:21.0±4.7µm3) of LBs per cell were decreased (p<0.008), but not total amount/ml lung volume (PBS:128±46.4x107µm3; rHuKGF:103±34.7x107µm3). This was paralleled by a shift to larger LBs. After rHuKGF, radiolabeled phospholipids accumulated in whole lung tissue relative to lavage fluid (p<0.01). However, less radiolabel was incorporated per cell (p<0.01). We conclude that under rHuKGF induced AEII-proliferation intracellular surfactant was decreased per single cell, whereas a constant amount was maintained per unit lung volume. We suggest that surfactant homeostasis is regulated at the level of phospholipid transport processes, as e.g. secretion and reuptake. Key words: surfactant, growth factors, proliferation, homeostasis
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