Neutrophil-activating properties of the melanoma growth-stimulatory activity.
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.
Moser
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B
Theodor-Kocher Institute, University of Bern, Switzerland.
Clark-Lewis
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I
Zwahlen
R
R
Baggiolini
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M
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000097:blood; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000235:genetics / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D007378:Interleukins / Q000235:genetics / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000138:chemical synthesis / Q000235:genetics / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010196:Pancreatic Elastase / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012689:Sequence Homology, Nucleic Acid; D012867:Skin / Q000187:drug effects / Q000473:pathology
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D007378:Interleukins; D009363:Neoplasm Proteins; D006861:Hydrogen Peroxide; D010196:Pancreatic Elastase; D002118:Calcium