Modulation of pulmonary alveolar type II cell phenotype and communication by extracellular matrix and KGF

• Published in: American Journal of Physiology: Cell Physiology 2001-10, Vol.281 (4), p.C1291-C1299
• Main Authors: Isakson, Brant E, Lubman, Richard L, Seedorf, Gregory J, Boitano, Scott
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - pharmacology; Animals; Calcium Signaling - drug effects; Calcium Signaling - physiology; Cell Communication - drug effects; Cell Communication - physiology; Cells, Cultured; Coloring Agents - pharmacokinetics; Connexin 26; Connexin 43 - analysis; Connexin 43 - biosynthesis; Connexins - analysis; Connexins - biosynthesis; Extracellular Matrix - physiology; Fibroblast Growth Factor 7; Fibroblast Growth Factors - pharmacology; Gap Junctions - physiology; Homeostasis - physiology; Male; Phenotype; Pulmonary Alveoli - chemistry; Pulmonary Alveoli - cytology; Rats; Rats, Sprague-Dawley; Uridine Triphosphate - pharmacology
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.2001.281.4.c1291

1  Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071-3166; and 2  Division of Pulmonary & Critical Care Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033 The alveolar epithelium consists of two cell types, alveolar type I (AT1) and alveolar type II (AT2) cells. We have recently shown that 7-day-old cultures of AT2 cells grown on a type I collagen/fibronectin matrix develop phenotypic characteristics of AT1 cells, display a distinct connexin profile, and coordinate mechanically induced intercellular Ca 2+ changes via gap junctions (25). In this study, we cultured AT2 cells for 7 days on matrix supplemented with laminin-5 and/or in the presence of keratinocyte growth factor. Under these conditions, cultured AT2 cells display AT2 type morphology, express the AT2-specific marker surfactant protein C, and do not express AT1-specific cell marker aquaporin 5, all consistent with maintenance of AT2 phenotype. These AT2-like cells also coordinate mechanically induced intercellular Ca 2+ signaling, but, unlike AT1-like cells, do so by using extracellular nucleotide triphosphate release. Additionally, cultured cells that retain AT2 cell-specific markers express connexin profiles different from cultured cells with AT1 characteristics. The parallel changes in intercellular Ca 2+ signaling with cell differentiation suggest that cell signaling mechanisms are an intrinsic component of lung alveolar cell phenotype. Because lung epithelial injury is accompanied by extracellular matrix and growth factor changes, followed by extensive cell division, differentiation, and migration of AT2 progenitor cells, we suggest that similar changes may be vital to the lung recovery and repair process in vivo. connexin; gap junction; keratinocyte growth factor; laminin-5; intercellular communication