Ocular expression of vascular cell adhesion molecule (VCAM-1) in 2-butoxyethanol-induced hemolysis and thrombosis in female rats.
We demonstrated previously that exposure of rats to 2-butoxyethanol (BE) was associated with morphological changes in red blood cells, hemolytic anemia, and disseminated thrombosis and infarction in different organs including the eyes. In order to elucidate the mechanism of thrombosis formation, we examined in this study the histology and immunohistochemical expression of vascular cell adhesion molecule-1 (VCAM-1), endothelial intercellular adhesion molecule-1 (ICAM-1), and P-selectin in the eyes of the female F344 rat exposed to 2, 3, or 4 daily doses of BE/250 mg/kg body weight. In this BE hemolysis and thrombosis model, positive VCAM-1 expression occurred only in eyes of rats exposed to 3 and 4 doses and was localized in the iris (epithelium lining the posterior surface, anterior mesenchymal epithelium), ciliary processes (lining epithelium, stromal cells), and retina (hypertrophic retinal pigment epithelium). Only weak immunolabeling was seen in eyes exposed to 2 doses. The appearance of VCAM-1 immunostaining correlated with the development of thrombosis located in the same structures. No change in ICAM-1 or P-selectin expression was seen. This immunolabeling distribution suggests that VCAM-1 functions in the pathogenesis of BE-related thrombosis by promoting adhesion of erythrocytes to the endothelium.
Nyska
Abraham
A
Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709-9998, USA. nyska@niehs.nih.gov
Moomaw
Cindy R
CR
Ezov
Nathan
N
Shabat
Shay
S
Levin-Harrus
Tal
T
Nyska
Meir
M
Redlich
Meir
M
Mittelman
Moshe
M
Yedgar
Saul
S
Foley
Julie F
JF
D000818:Animals; D004195:Disease Models, Animal; D005026:Ethylene Glycols / Q000633:toxicity*; D005123:Eye / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006461:Hemolysis / Q000187:drug effects*; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012166:Retinal Hemorrhage / Q000139:chemically induced / Q000473:pathology; D012997:Solvents / Q000633:toxicity*; D013927:Thrombosis / Q000139:chemically induced* / Q000473:pathology; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D005026:Ethylene Glycols; D019007:P-Selectin; D012997:Solvents; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C017096:n-butoxyethanol