Rapamycin administration significantly reduced the arterial proliferative response after PTCA in the pig by increasing the level of the CDKI p27(kip1) and inhibition of the pRb phosphorylation within the vessel wall. Therefore, pharmacological interventions that elevate CDKI in the vessel wall and target cyclin-dependent kinase activity may have a therapeutic role in the treatment of restenosis after angioplasty in humans.

No abstract

Secretory granules of the rat basophilic leukemia (RBL-1) cell, a chemically-generated tumor cell line maintained in tissue culture, were shown to stain with alcian blue but not with safranin counterstain and to have sparse, small, electron-dense granules. A Mr 25,000 protein was the major [3H]diisopropyl fluorophosphate-binding protein in extracts of RBL-1 cells. Double-immunodiffusion analysis of extracts revealed immunoreactivity for rat mast cell protease (RMCP)-II, a Mr 25,000 neutral protase present in the secretory granules of rat mucosal mast cells and cultured rat bone marrow-derived mast cells, but no immunoreactivity for RMCP-I, the predominant neutral protease of rat connective tissue mast cells. By radial immunodiffusion, there was 66.8 ng of RMCP-ll per 106 cells. Whereas rat connective tissue mast cells stain with alcian blue and safranin and contain heparm proteoglycan, rat mucosal and rat bone marrow-derived mast cells stain with alcian blue only and contain a non-heparin proteoglycan and lesser amounts of histamine. Proliferation of rat mucosal mast cells in vivo and rat bone marrowderived mast cells in vitro requires T-cell factors, whereas no comparable requirement has been observed for connective tissue mast cells. The transformed RBL-1 tumor cell, whose growth is independent of factors other than those present in standard tissue culture medium, has previously been shown to contain predominantly chondroitin sulfate di-B proteoglycans and low amounts of histamine. The similar histology and secretory granule biochemistry of the rat mucosal mast cell, rat culture-derived mast cell, and RBL-1 cell suggest that they comprise a single mast cell subclass distinct from the rat connective tissue mast cell. (6)(7)(8)(9). Both of these rat mast cell subclasses can be activated with IgE and specific antigen. The connective tissue cell also responds to compound 48/80, (a condensation product of N-methyl-pmethoxyphenethylamine and formaldehyde), whereas the mucosal mast cell in situ (10) or isolated from intestine (11) does not. Disodium cromoglycate and theophylline inhibit the activation of the connective tissue mast cell but not of the mucosal mast cell (12). Homogeneous populations of mast cells resembling the mucosal mast cell subclass have been obtained in vitro from rat bone marrow cultured in the presence of conditioned medium from antigen-activated immune mesenteric lymph nodes (13,14). These mast cells stain with alcian blue but not safranin, have low amounts of histamine, contain RMCP-II, and appear to have a non-heparin proteoglycan (15).Thymic-dependent proliferation of mast cells also occurs in the mucosa of helminth-infected mice (16), and mouse hematopoietic stem cells cultured in vitro in the presence of lymphocyte conditioned medium differentiate into mast cells resembling the mucosal mast cell subclass (17-22). The cultured cells depend on the T-cell lymphokine interleukin 3 for growth (23) and contain an oversulfated chondroitin sulfate proteoglycan, termed chondroitin sulfate...

These findings suggest that TMAO slows aortic lesion formation in this mouse model and may have a protective effect against atherosclerosis development in humans.