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1 Department of Anatomy, Physiology & Cell Biology, School of Veterinary Medicine, University of California, Davis, School of Veterinary Medicine, Davis, CA, USA
2 Department of Anatomy, Physiological Sciences & Radiology, College of Veterinary Medicine, Raleigh, NC, USA
* To whom correspondence should be addressed. E-mail: mevans{at}ucdavis.edu.
Development of the basement membrane zone (BMZ) occurs postnatally in the rhesus monkey. The purpose of this study was to determine whether house dust mite allergen (HDMA) plus ozone altered this process. Rhesus monkeys were exposed to a regimen of HDMA and or ozone or filtered air (FA) for 6 months. To detect structural changes in the BMZ we measured immunoreactivity of collagen I. To detect functional changes in the BMZ we measured perlecan and fibroblast growth factor-2 (FGF-2). We also measured components of the FGF-2 ternary signaling complex, (fibroblast growth factor receptor-1 (FGFR-1) and syndecan-4). The width of the BMZ was irregular in the ozone groups suggesting atypical development of the BMZ. Perlecan was also absent from the BMZ. In the absence of perlecan, FGF-2 was not bound to the BMZ. However FGF-2 immunoreactivity was present in basal cells, the lateral intercellular (LIS)and attenuated fibroblasts. FGFR-1 immunoreactivity was down regulated and syndecan-4 immunoreactivity was up regulated in the basal cells. This suggests that FGF-2 in basal cells and LIS may be bound to the syndecan-4. We conclude that ozone and HDMA + ozone effected incorporation of perlecan into the BMZ resulting in atypical development of the BMZ. These changes are associated with specific alterations in the regulation of FGF-2, FGFR-1 and syndecan-4 in the airway epithelial-mesenchymal trophic unit, which may be associated with the developmental problems of the lung associated with exposure to ozone.
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