Effects of Amrinone on Thrombin-Induced Platelet-Derived Growth Factor-Like Protein Secretion from Endothelial Cells

Shaddy, Robert E.; Paisley, J E; Hansen, J. C.

doi:10.1203/00006450-199110000-00011

Cited by 5 publications

(4 citation statements)

References 17 publications

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“…This results in an amplification of the infiltration of immunocompetent cells. Furthermore, the T cells force a stimulation of PDGF synthesis in endothelial cells [23]. IFN-g leads to an activation of macrophages, which then produce an increased amount of cytokines (IL-6, IL-1, tumour necrosis factor (TNF)-a and PDGF).…”

Section: Discussionmentioning

confidence: 99%

The role of platelet derived growth factor in endomyocardial biopsies shortly after heart transplantation in relation to postoperative course

Sack

Vielfort

Koch

et al. 2004

European Journal of Cardio-Thoracic Surgery

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Section: Discussionmentioning

confidence: 99%

The role of platelet derived growth factor in endomyocardial biopsies shortly after heart transplantation in relation to postoperative course

Sack

Vielfort

Koch

et al. 2004

European Journal of Cardio-Thoracic Surgery

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“…Residual PDGF-like protein initially present in the FCS at the time of the initiation of CMV infection could have still been present in the medium at the time of removal of the conditioned medium. This could have accounted for the somewhat elevated absolute levels of control PDGF-like protein production (12-13 fmol/10~ EC) compared with previously reported baseline values of 5-6 fmol110~ EC in previous experiments from this laboratory, in which plasma-derived serum was used instead of FCS (31). However, it is also possible that the prolonged incubation time of the EC in this experiment (5.4 2 1.8 d) may also account for the increased expression of PDGF-like protein.…”

Section: Discussionmentioning

confidence: 68%

“…PDGF-like protein secretion from EC. EC-conditioned medium was collected from the EC monolayers and assayed for the presence of PDGF-like protein using a 1 2 5~-~~~~ (PDGF, Inc., Boston, MA) competitive radioreceptor binding assay as previously described (31). Medium used for collection and analysis of PDGF-like protein was standard EC growth medium that contained FCS at the onset of experiments and then became gradually depleted of serum by the EC during continued culture and incubation at 37OC over the ensuing 5.4 + 1.8 d. Identical media were used in both sets of control cells (UV-irradiated viruslsham-infected EC and untreated EC), which were cultured in parallel with test plates under identical conditions.…”

Section: Methodsmentioning

confidence: 99%

Effects of Cytomegalovirus Infection on Growth Factor Production in Endothelial Cells and Fibroblasts

et al. 1995

Pediatr Res

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To determine whether cytomegalovirus (CMV) infection alters growth factor production from endothelial cells (EC) or fibroblasts, we infected human umbilical vein EC with CMV VHL/E, a strain of CMV with affinity for human EC, and we infected human foreskin fibroblasts with CMV AD169. CMV caused cytopathic effect and positive CMV staining by immunofluorescence within 5 d, effects not seen in cells infected with UV-irradiated CMV or in uninfected (control) cells. The supernatants from the EC were assayed for platelet-derived growth factor (PDGF)-like protein using a radioreceptor inhibition assay, and EC and fibroblasts were assayed for basic fibroblast growth factor (bFGF) by Western blot analysis. There were no significant differences in PDGF production between groups of EC: CMV-infected EC, 13.5 +/- 2.6; UV-irradiated infected EC, 12.1 +/- 3.6; control EC, 12.9 +/- 1.7 fmol/10(6) EC (mean +/- SD, n = 10, p = NS). There were also no significant differences in bFGF production between CMV-infected EC, UV-irradiated infected EC, and control EC as evidenced by similar intensity of migration of bFGF as a single band at approximately 18 kD (n = 5). In contrast, CMV infection of fibroblasts induced a shift in production of bFGF to higher molecular weight forms migrating at 24 and 26 kD molecular mass. alpha-Interferon failed to alter bFGF production. We conclude that CMV VHL/E infection of EC does not directly alter PDGF or bFGF production from EC. However, CMV infection of cultured human fibroblasts qualitatively alters bFGF by inducing a shift to higher molecular weight forms.

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“…In addition, previous research has shown that amrinone inhibits the release of thrombin-induced. platelet-derived growth factor-like protein from human endothelial cells [22]. The endothelial stabilizing effect may also play a role in promoting allograft survival, since severe vasculitis was observed in the 10-day-oId cardiac allografls (Fig.2c).…”

Section: Discussionmentioning

confidence: 93%

Beneficial effect of amrinone on murine cardiac allograft survival

Hirozane

Matsumori

Furukawa

et al. 1995

Clinical and Experimental Immunology

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SUMMARYAmrinone is a non-glycoside positive inotropic agent with an inhibitory effect on a cyclic adenosine monophosphate (AMP) phosphodiesterase isoenzyme. In the present study, we examined the immunosuppressive action of amrinone, since several other cyclic AMP-elevating agents have been shown to suppress T lymphocyte activation. First, the in vivo effects of amrinone were investigated. Oral amrinone treatment, at 40 mg/kg per day, significantly prolonged median cardiac allograft survival compared with non-treated controls (22-0 days versus 10-5 days, P< 0-01) when DBA/2 mouse hearts (H-2d) were heterotopically transplanted into C57B1/6 mice (H-2b). Histopathological examination showed that there was less prominent cellular infiltration in the amrinonetreated than in the non-treated allografts. Plasma amrinone concentrations of mice after a single oral dose of 40 mg/kg were within the range of clinical relevance. To clarify the mechanism of action, in vitro studies were done. The generation of specific cytotoxic T lymphocytes after mixed lymphocyte culture was significantly suppressed by addition of amrinone to the culture medium at 5,ug/ml. The production of IL-2 and the interferon-gamma during mixed lymphocyte culture was also suppressed by amrinone at 5 ag/ml. However, the level of intracellular cyclic AMP in mouse splenic lymphocytes was not affected significantly by the same dose of amrinone. In conclusion, amrinone has immunosuppressive actions at the therapeutic doses, and it may be a beneficial agent for therapy against acute cardiac allograft rejection.

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Effects of Amrinone on Thrombin-Induced Platelet-Derived Growth Factor-Like Protein Secretion from Endothelial Cells

Cited by 5 publications

References 17 publications

The role of platelet derived growth factor in endomyocardial biopsies shortly after heart transplantation in relation to postoperative course

The role of platelet derived growth factor in endomyocardial biopsies shortly after heart transplantation in relation to postoperative course

Effects of Cytomegalovirus Infection on Growth Factor Production in Endothelial Cells and Fibroblasts

Beneficial effect of amrinone on murine cardiac allograft survival

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