Clara cell secretory protein; a determinant of pcb bio-accumulation
within mammals.
Stripp, Barry R., Johan Lund, Gregory W. Mango, Kurt C. Doyen, Carl
Johnston, Kjell Hultenby, Magnus Nord, and Jeffrey A. Whitsett.
Division of Pulmonary Biology, Department of Pediatrics, Children's
Hospital Medical Center, Cincinnati, Ohio 45229, USA, Departments of
Environmental Medicine and Pediatrics, School of Medicine and
Dentistry, University of Rochester, Rochester, NY 14642, USA,
Department of Medical Nutrition, Karolinska Institute, Huddinge
University Hospital F60 Novum, S-141 86 Huddinge, Sweden
APStracts 3:0104L, 1996.
Clara cell secretory protein (CCSP) is a product of nonciliated cells
of the conducting airway epithelium. The normal physiologic function
of CCSP is unknown. However, the ability of CCSP to bind small
lipophilic molecles such as steroid hormones and certain pollutants
has led to speculation that this protein may mediate the biological
accumulation of potentially harmful polychlorinated biphenyl (PCB)
metabolites within the lung. To investigate the contribution of CCSP
in the in vivo accumulation of methylsulfonyl-PCB's, a line of mice
was established that were homozygous for a null allele of the CCSP
gene. Clara cell secretory protein deficient mice were healthy and
fertile with no gross physiologic or pathologic abnormalities.
Parenteral challenge with the PCB metabolite 4-(methylsulfonyl), 2,
2', 4', 5, 5'-pentachlorobiphenyl ((MeSO2)-PCB) demonstrated that
CCSP deficient mice no longer accumulate this class of pollutants
within lung and kidney tissues. These data demonstrate that CCSP is
the determinant for (MeSO2)-PCB accumulation within mice and support
the notion that bioconcentration of (MeSO2)-PCB pollutants occurs at
sites of CCSP localization, such as the respiratory and reproductive
tracts of humans.
Received 26 December 1995; accepted in final form 2 May 1996.
APS Manuscript Number L379-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96