Abstract
Melanoma growth-stimulatory activity (MGSA), a peptide reported to be mitogenic for Hs294T human melanoma cells, has extensive sequence similarity to the neutrophil-activating peptide NAP-1/IL-8, suggesting functional similarities. To test this hypothesis, MGSA was chemically synthesized and tested for its effects on human neutrophils. It was found to induce chemotaxis, exocytosis of elastase, and changes in cytosolic-free calcium to an extent and at concentrations similar to NAP-1/IL-8. However, MGSA was considerably less potent than NAP-1/IL-8 in inducing the respiratory burst. Intradermal injections in rats of MGSA resulted in a massive accumulation of neutrophils. Our data demonstrate that, apart from its growth-stimulatory activity, MGSA is a potent inflammatory agonist with neutrophil-stimulating properties.
Full Text
The Full Text of this article is available as a PDF (379.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anisowicz A., Bardwell L., Sager R. Constitutive overexpression of a growth-regulated gene in transformed Chinese hamster and human cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7188–7192. doi: 10.1073/pnas.84.20.7188. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Anisowicz A., Zajchowski D., Stenman G., Sager R. Functional diversity of gro gene expression in human fibroblasts and mammary epithelial cells. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9645–9649. doi: 10.1073/pnas.85.24.9645. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baggiolini M., Walz A., Kunkel S. L. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989 Oct;84(4):1045–1049. doi: 10.1172/JCI114265. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clark-Lewis I., Aebersold R., Ziltener H., Schrader J. W., Hood L. E., Kent S. B. Automated chemical synthesis of a protein growth factor for hemopoietic cells, interleukin-3. Science. 1986 Jan 10;231(4734):134–139. doi: 10.1126/science.3079915. [DOI] [PubMed] [Google Scholar]
- Clark-Lewis I., Hood L. E., Kent S. B. Role of disulfide bridges in determining the biological activity of interleukin 3. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7897–7901. doi: 10.1073/pnas.85.21.7897. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clark-Lewis I., Lopez A. F., To L. B., Vadas M. A., Schrader J. W., Hood L. E., Kent S. B. Structure-function studies of human granulocyte-macrophage colony-stimulating factor. Identification of residues required for activity. J Immunol. 1988 Aug 1;141(3):881–889. [PubMed] [Google Scholar]
- Colditz I., Zwahlen R., Dewald B., Baggiolini M. In vivo inflammatory activity of neutrophil-activating factor, a novel chemotactic peptide derived from human monocytes. Am J Pathol. 1989 Apr;134(4):755–760. [PMC free article] [PubMed] [Google Scholar]
- Dewald B., Thelen M., Wymann M. P., Baggiolini M. Staurosporine inhibits the respiratory burst and induces exocytosis in human neutrophils. Biochem J. 1989 Dec 15;264(3):879–884. doi: 10.1042/bj2640879. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lindley I., Aschauer H., Seifert J. M., Lam C., Brunowsky W., Kownatzki E., Thelen M., Peveri P., Dewald B., von Tscharner V. Synthesis and expression in Escherichia coli of the gene encoding monocyte-derived neutrophil-activating factor: biological equivalence between natural and recombinant neutrophil-activating factor. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9199–9203. doi: 10.1073/pnas.85.23.9199. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peveri P., Walz A., Dewald B., Baggiolini M. A novel neutrophil-activating factor produced by human mononuclear phagocytes. J Exp Med. 1988 May 1;167(5):1547–1559. doi: 10.1084/jem.167.5.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Richmond A., Balentien E., Thomas H. G., Flaggs G., Barton D. E., Spiess J., Bordoni R., Francke U., Derynck R. Molecular characterization and chromosomal mapping of melanoma growth stimulatory activity, a growth factor structurally related to beta-thromboglobulin. EMBO J. 1988 Jul;7(7):2025–2033. doi: 10.1002/j.1460-2075.1988.tb03042.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schröder J. M., Mrowietz U., Christophers E. Purification and partial biologic characterization of a human lymphocyte-derived peptide with potent neutrophil-stimulating activity. J Immunol. 1988 May 15;140(10):3534–3540. [PubMed] [Google Scholar]
- Wen D. Z., Rowland A., Derynck R. Expression and secretion of gro/MGSA by stimulated human endothelial cells. EMBO J. 1989 Jun;8(6):1761–1766. doi: 10.1002/j.1460-2075.1989.tb03569.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Westwick J., Li S. W., Camp R. D. Novel neutrophil-stimulating peptides. Immunol Today. 1989 May;10(5):146–147. doi: 10.1016/0167-5699(89)90164-3. [DOI] [PubMed] [Google Scholar]
- Wymann M. P., von Tscharner V., Deranleau D. A., Baggiolini M. Chemiluminescence detection of H2O2 produced by human neutrophils during the respiratory burst. Anal Biochem. 1987 Sep;165(2):371–378. doi: 10.1016/0003-2697(87)90284-3. [DOI] [PubMed] [Google Scholar]
- von Tscharner V., Deranleau D. A., Baggiolini M. Calcium fluxes and calcium buffering in human neutrophils. J Biol Chem. 1986 Aug 5;261(22):10163–10168. [PubMed] [Google Scholar]