THE EFFECT OF α-MELANOCYTE STIMULATING HORMONE ON BURN-INDUCED OXIDANT PRODUCTION BY RAT PERITONEAL NEUTROPHILS

THE EFFECT OF α-MELANOCYTE STIMULATING HORMONE ON BURN-INDUCED OXIDANT PRODUCTION BY RAT PERITONEAL NEUTROPHILS

Objective: Previous findings related to the anti-inflammatory effects of α-melanocyte stimulating hormone (α-MSH) indicate that the peptide might inhibit inflammation by antagonizing the effects of local cytokines or by inhibiting neutrophil functions. In addition, it is a potent inhibitor of the induction of the inducible nitric oxide synthase (iNOS) in cultured macrophages and of nitric oxide (NO) production in a sepsis model. This study was designed to investigate whether α-MSH affects reactive oxygen metabolite production by rat peritoneal neutrophils following burn injury and whether NO is involved in this effect.Methods: The neutrophils were removed from the peritoneum of the rats 6 h after burn or sham trauma. Cells (2 X 106 /ml) were treated with the increasing concentrations of α-MSH (10–12 M, 10–10 M, 10–8 M or 10–6 M). Nitric oxide donor, sodium nitroprusside ranging from (10–10 - 10–4 M) was added to the cells in the presence of α-MSH. Reactive oxygen metabolite production was measured by chemiluminescence (CL) technique using luminol or lucigenin probes.Results: Lucigenin CL value of cells obtained from burn animals was significantly higher than those obtained from the sham group. α-MSH caused significant reductions in high lucigenin CL values and this effect was partly inhibited by sodium nitroprusside.Conclusion: Our results suggest that α-MSH is effective in preventing oxidant production by neutrophils activated by burn trauma, at least in part, by a mechanism involving nitric oxide. 

___

  • Catania A, Lipton JM. Alpha-melanocyte stimulating hormone in the modulation of host reactions. Endocr Rev 1993; 14: 54-57.
  • Catania A, Rajora hi, Capsoni, F, Minonzio F, Star RA, Lipton JM. The neuropeptide a-MSH has specific receptors on neutrophils and reduces chemotaxis in vivo. Peptides 1996; 17: 675-679.
  • Mason MJ, Van Epps D. Modulation of IL-1, tumor necrosis factor, and C5a-mediated murine neutrophil migration by alpha- melanocyte stimulating hormone. J Immunol 1989; 142: 1646-1651.
  • Perretti M, Appleton I, Parente L, Flower RJ. Pharmacology of interleukin-1 -induced neutrophil migration. Agents Actions 1993; 38: C64-65.
  • Rajora Fi, Ceriani G, Catania A, Star RA, Murphy MT, Upton JM. a-MSH production, receptors, and influence on neopterin, in a human monocyte/macrophage cell Une. J Leukocyte Biol 1996; 59: 248-253.
  • Star RA, Rajora Id, Huang J, Stock RC, Catania A, Lipton JM. Evidence of autocrine modulation of macrophage nitric oxide synthase by a-MSH. Proc HatI Acad Sci USA 1995; 92: 8016-8020.
  • Jones II WG, Minei JP, Barber AE, Fahey III TJ, Shires III GT, Shires GT. Splancnic vasoconstriction and bacterial translocation after thermal trauma. Am J Physiol 1991 ; 261 : HI 190-H1 196.
  • Morris SE, Havaratnam H, Townsend CM, Herndon DH. A comparison of the effect of thermal injury and smoke inhalation on bacterial translocation. J Trauma 1990; 30: 639-643.
  • Youn YR, LaLonde C, Demling R. The role of mediators in the response to thermal injury. World J Surg 1992; 16: 30-36.
  • Chen LW, Hsu CM, Cha MC, Chen JS, Chen SC. Changes in gut mucosal nitric oxide synthase (HOS) activity after thermal injury and its relation with barrier failure. Shock 1999; I I: 104-1 10.
  • Chen LW, Hsu CM, Wang JS, Chen JS, Chen SC. Specific inhibition of ¡HOS decreases the intestinal mucosal peroxynitrite level and improves the barrier function after thermal injury. Burns 1998; 24: 699-705.
  • Rrawisz JE, Sharon P, Stenson W F. Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Gastroenterology 1984; 87: 1344- 1350.
  • Haklar G, Özveri ES, Yüksel M, Aktan AÖ, Yalçın /IS. Different kinds of reactive oxygen and nitrogen species were detected in colon and breast tumors. Cancer Letters 2001; 165: 219-224.
  • Davies GR, Simmonds HJ, Stevens TR, et at. Helicobacter pylori stimulates antral mucosal reactive oxygen metabolite production in vivo. Gut 1994:35: 179-185.
  • Ohara Y, Peterson TE, Harrison DG. Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest 1993; 91: 2546-2551.
  • Clancy RM, Leszczynska-Piziak J, Abramson SB. Hitric oxide, an endothelial cell relaxation factor, inhibits neutrophil superoxide production via a direct action on the HADPH oxidase. J Clin Invest 1992; 90: 1116-1121.