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Response of microvascular endothelial cells to biological response modifiers
Author(s) -
Hicks C,
Breit SN,
Penny. R
Publication year - 1989
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.1989.41
Subject(s) - retinoic acid , cytotoxic t cell , tumor necrosis factor alpha , cell growth , microbiology and biotechnology , growth factor , thymidine , biological response modifiers , chemistry , lymphokine , cytokine , immunology , in vitro , biology , cell culture , biochemistry , immune system , receptor , genetics
Summary This study investigated in vitro biological response modifiers (BRM) possibly involved in initiation and regulation of human capillary endothelial cell (HCEC) growth. An indicator assay was developed using tritiated thymidine to measure increased DNA turnover. Purified or recombinant BRMs tested singly and in combination included: interferon (IFN; α and γ), tumour necrosis factor (TNF; α and β), transforming growth factor (TGF: α and β). rIL‐1, rIL‐2, pIL‐2, platelet derived growth factor (PDGF) and retinoic acid. Under limiting serum conditions only rlL‐2 (≥ 10 U/mL) caused proliferation of the cells. γIFN together with TNFα(500 U/mL of each) was cytotoxic. Under maximal stimulus conditions, a cytostatic effect resulted from exposing HCEC to: α or γ IFN (≥ 1000 U/mL), TGFβ (≥5 ng/mL), rIL‐1 (≥ 0·5 U/mL) and rIL‐1 plus γIFN, γIFN (500 U/mL) plus TNFα exhibited synergism in the Inhibition of proliferation and produced a cytotoxic effect at TNFα concentrations ≥500 U/mL. By contrast, rIL‐2 enhanced proliferation at >5 U/mL. When rIL‐2 was combined with γIFN, an inhibitory effect on proliferation was observed, although to a lesser extent than γIFN alone. Pretreating the cells with 100 U/mL γIFN prior to rIL‐1 or IL‐2 exposure produced no change in the trends observed above. TGFα also stimulated cell proliferation at concentrations ≥0·5 ng/mL. PDGF and retinoic acid had no effect on proliferation in the concentration range 0·5‐10 U/mL. By investigating the response of HCEC to these BRMs, the nature of, and response to the signals from immune cells in inflammatory disease processes can be better understood.