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Effects of T cells on platelet-derived growth factor-like protein secretion from endothelial cells
R E Shaddy1, J C Hansen, C G Cowley
1Department of Pediatrics, University of Utah School of Medicine, Salt Lake City.
The cause of accelerated graft arteriosclerosis after heart transplantation is unknown. To examine whether the interactions of T cells and endothelial cells (ECs) could contribute to the cause of this phenomenon, T cells were co-incubated with human umbilical artery endothelial cells (HUAEC) and human vein endothelial cells (HUVEC) and the resulting conditioned medium supernatant was assayed for the presence of platelet-derived growth factor (PDGF)-like protein. PDGF-like protein secretion was significantly greater from HUAECs co-incubated with T cells at T-cell/HUAEC ratios of 30:1 (6.9 +/- 1.1 fmol/10(6) ECs) and 10:1 (6.0 +/- 1.1 fmol/10(6) ECs) than the combined background secretion from HUAECs and T cells incubated separately (3.6 +/- 0.8 fmol/10(6) ECs) (p less than 0.05). PDGF-like protein secretion above background levels from HUAECs was significantly greater, however, than from HUVECs co-incubated with T cells at T-cell/HUVEC ratios of 30:1 (1.0 +/- 0.4 fmol/10(6) ECs) and 10:1 (0.75 +/- 0.36 fmol/10(6) ECs) (p less than 0.05). In four experiments, preincubation of HUAECs with gamma-interferon induced HLA-DR antigen expression but actually caused a decrease in T-cell-induced PDGF-like protein secretion above background levels (3.0 +/- 0.6 fmol/10(6) ECs) when compared to nonstimulated HUAECs (4.0 +/- 0.4 fmol/10(6) ECs; p less than 0.05). PDGF-like protein secretion was minimal at 1 hour and increased over time to a maximum at 24 hours. The conclusion is that T cells are capable of inducing secretion of a very potent mitogen, PDGF-like protein, from endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
The cause of accelerated graft arteriosclerosis after heart transplantation is unknown. To examine whether the interactions of T cells and endothelial cells (ECs) could contribute to the cause of this phenomenon, T cells were co-incubated with human umbilical artery endothelial cells (HUAEC) and human vein endothelial cells (HUVEC) and the resulting conditioned medium supernatant was assayed for the presence of platelet-derived growth factor (PDGF)-like protein. PDGF-like protein secretion was significantly greater from HUAECs co-incubated with T cells at T-cell/HUAEC ratios of 30:1 (6.9 +/- 1.1 fmol/10(6) ECs) and 10:1 (6.0 +/- 1.1 fmol/10(6) ECs) than the combined background secretion from HUAECs and T cells incubated separately (3.6 +/- 0.8 fmol/10(6) ECs) (p less than 0.05). PDGF-like protein secretion above background levels from HUAECs was significantly greater, however, than from HUVECs co-incubated with T cells at T-cell/HUVEC ratios of 30:1 (1.0 +/- 0.4 fmol/10(6) ECs) and 10:1 (0.75 +/- 0.36 fmol/10(6) ECs) (p less than 0.05). In four experiments, preincubation of HUAECs with gamma-interferon induced HLA-DR antigen expression but actually caused a decrease in T-cell-induced PDGF-like protein secretion above background levels (3.0 +/- 0.6 fmol/10(6) ECs) when compared to nonstimulated HUAECs (4.0 +/- 0.4 fmol/10(6) ECs; p less than 0.05). PDGF-like protein secretion was minimal at 1 hour and increased over time to a maximum at 24 hours. The conclusion is that T cells are capable of inducing secretion of a very potent mitogen, PDGF-like protein, from endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)