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KMID : 0390019930030020064
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Pediatric Allergy and Respiratory Disease
1993 Volume.3 No. 2 p.64 ~ p.73
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Substance P Augments TNF Production in Human Monocytes Derived Macrophages
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Abstract
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Substance P(SP) is an undecapeptide of aminoacid sequence (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Gly-Leu-Met-NH2) that belongs to a family of structually related peptides known as tachykinins and is widely distributed in the central nervous system. SP is
involved
in biological activities of cells in the immune system including induction of cytokines in immune cells.
We have investigated the effects of SP on constitutive and/or lipopolysaccharides(LPS)-induced expression of tumor necrosis factor(TNF) in cultured blood nonocyte-derived macrophages(MDM). Cells cultured in vitro for 14 days were treated with SP
or
SP
fragments(SP1-4 and SP5-110 at various concentrations(10E-10 to 10E-6M) in the presence or absence of LPS before harvesting culture supernatants. TNF bioactivity in culture supernatnats were mesured with the L929 cell line.
The MDM from ten of twelve donors showed significant production of TNF by the treatment of SP alone. SP and LPS also interact in a synergistic fashion in upregulating TNF production on MDM from responders. The stimulatory effect of SP was
inhibited
by
two SP antagonists, spantide ([D-Arg1, D-Trp7, 9,Leu11]-SP and CP-96.345(a non-peptide antagonist of the SP receptor). In addition, an anti-SP polyclonal antibody blocked the SP effect on the TNF production in the cultured MDM, further indicating
the
specificity of these effects. These results demonstrate that SP is an important regulator of monokine production in human monocytes/macrophages.
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KEYWORD
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