Atypical development of the tracheal basement membrane zone of infant rhesus monkeys exposed to ozone and allergen.
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 for 6 mo. 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 space (LIS), and attenuated fibroblasts. FGFR-1 immunoreactivity was downregulated, and syndecan-4 immunoreactivity was upregulated 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 plus 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 lungs associated with exposure to ozone.
Evans
Michael J
MJ
Dept. of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, Univ. of California, Davis, CA 95616, USA. mevans@ucdavis.edu
Fanucchi
Michelle V
MV
Baker
Gregory L
GL
Van Winkle
Laura S
LS
Pantle
Lorraine M
LM
Nishio
Susan J
SJ
Schelegle
Edward S
ES
Gershwin
Laurel J
LJ
Miller
Lisa A
LA
Hyde
Dallas M
DM
Sannes
Philip L
PL
Plopper
Charles G
CG
D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D001485:Basement Membrane / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D004338:Drug Combinations; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000378:metabolism; D010126:Ozone / Q000494:pharmacology*; D011509:Proteoglycans / Q000378:metabolism; D039981:Pyroglyphidae / Q000276:immunology*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D053671:Syndecan-4; D014132:Trachea / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism
D000485:Allergens; D024042:Collagen Type I; D004338:Drug Combinations; D019812:Heparan Sulfate Proteoglycans; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D017468:Receptors, Fibroblast Growth Factor; D053671:Syndecan-4; D016222:Fibroblast Growth Factor 2; C071927:perlecan; D010126:Ozone; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1