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Published ahead of print on August 1, 2002, doi:10.1164/rccm.200204-285OC

Am. J. Respir. Crit. Care Med., Volume 166, Number 11, December 2002, 1498-1509

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Submitted on April 4, 2002
Accepted on July 25, 2002

Secretoglobins SCGB3A1 and SCGB3A2 Define Secretory Cell Subsets in Mouse and Human Airways

Susan D Reynolds1, Paul R Reynolds1*, Gloria S Pryhuber2, Jonathan D Finder3, and Barry R Stripp1

1 Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA, 2 Department of Pediatrics, University of Rochester, Rochester, NY, USA, 3 Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA

* To whom correspondence should be addressed. E-mail: preynolds{at}server.ceoh.pitt.edu.

Clara cell secretory protein (CCSP) is expressed abundantly within the conducting airway epithelium and is thought to have immunoregulatory functions. Differences in the localization of CCSP between mouse and human airways led us to hypothesize that functional homologues of CCSP may compensate for the lack of CCSP expression in proximal airway locations. We previously identified an expressed sequence tag (EST-W82219) whose expression is induced within Clara cells of CCSP knockout mice. EST-W82219 is distantly related to CCSP and represents the first member of a new sub-family of secretoglobins (MmSCGB3A1). Another member of the mouse SCGB3 family (MmSCGB3A2) as well as human orthologues (HsSCGB3A1 and HsSCGB3A2) were identified that possess structural homology to CCSP, suggesting they may share common functional properties. SCGB3A2 mRNA localizes to a subset of SCGB3A1 expressing cells within bronchi of both mouse and neonatal human lungs. CCSP, SCGB3A1, and SCGB3A2 were decreased in airways of neonates with bronchopulmonary dysplasia and in mice following airway injury. We conclude that secretory cells of the conducting airway epithelium express distinct members of the secretoglobin family in a partially overlapping fashion. Altered expression of secretoglobins in airway disease may contribute to immunoregulatory perturbations commonly seen in chronic airway disease
Key words: CCSP, Heterogeneity, Clara cells, bronchopulmonary dysplasia, immunoregulatory




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