Balloon catheter de-endothelialization of the nude rat carotid. Response to injury in the absence of functional T lymphocytes.
The development of an intimal proliferative lesion after balloon catheter de-endothelialization was studied in congenitally athymic nude rats lacking T lymphocytes. Significant intimal thickening was observed in both the homozygous (nu/nu) and euthymic heterozygous (nu/+) animals 6 days after injury, which increased further after 10 days. There was no significant difference in mean intimal:medial cross-sectional area between the nu/nu and nu/+ animals at either time. Approximately 1% of the cells in the neointima of both groups of animals were leukocytes (OX-1 positive); 0.7% were macrophages (ED-1 positive). In neither nu/nu nor nu/+ animals did T lymphocytes (OX-19-positive cells) constitute more than 0.1% of the neointimal cell population. These data suggest that T lymphocytes do not play a significant role in the accumulation of neointimal cells. The presence of macrophages within the lesions raises the possibility that they may be involved in the recruitment and proliferation of smooth muscle cells. In vitro characterization of nu/nu carotid medial smooth muscle cells demonstrated approximately 500,000 binding sites for platelet-derived growth factor (PDGF)-BB and few PDGF-AA binding sites (less than 10,000). The mitogenic and chemotactic responses of these cells to the three dimeric forms of PDGF correlated with this receptor subunit distribution. Platelet-derived growth factor accounted for approximately 50% of the mitogenic activity of a rat platelet releasate. Platelet-derived growth factor-BB and PDGF-AB were both potent chemotactic agents for the nude rat carotid smooth muscle cells with a peak response at approximately 10 ng/ml. In contrast, PDGF-AA, transforming growth factor beta, and basic fibroblast growth factor were only weak chemoattractants for these cells.
Ferns
G A
GA
Department of Pathology, University of Washington, Seattle 98195.
Reidy
M A
MA
Ross
R
R
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002339:Carotid Arteries / Q000473:pathology / Q000503:physiopathology; D020212:Carotid Artery Injuries; D002404:Catheterization; D004730:Endothelium, Vascular / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D006133:Growth Substances / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008934:Mitogens / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D011923:Rats, Nude; D011956:Receptors, Cell Surface / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor; D013601:T-Lymphocytes / Q000502:physiology; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology
D006133:Growth Substances; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D017479:Receptors, Platelet-Derived Growth Factor; D013917:Thrombin