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Sulochrin inhibits eosinophil activation and chemotaxis.

AbstractOBJECTIVE:
Because eosinophils likely play important roles in the pathophysiology of allergic diseases, specific inhibitors of eosinophils may be desirable to treat such diseases. To evaluate the capacity of a novel compound, sulochrin, as an inhibitor of eosinophilic inflammation, we examined the effects of this compound on various effector functions of eosinophils.
MATERIALS AND METHODS:
We examined the effects of sulochrin on degranulation of human eosinophils stimulated with platelet-activating factor (PAF) or Sepharose 4B beads coated with secretory IgA (sIgA) or IgG. The effects of sulochrin on other effector functions of human eosinophils, including superoxide anion (O2-) production, leukotriene (LT) C4 release, and interleukin (IL)-8 production induced by sIgA-beads were also studied. Finally, using PAF and LTB4 as chemoattractants, we evaluated the potency of sulochrin to inhibit eosinophil migration in vitro and in vivo.
RESULTS:
Sulochrin inhibited EDN release by eosinophils stimulated with sIgA-beads. IgG-beads and PAF in a concentration-dependent manner; IC50 values were 0.75 microM, 0.30 microM and 0.03 microM. Eosinophil O2- production, LTC4 release, and IL-8 production were also inhibited by sulochrin. Furthermore, PAF-induced chemotaxis of human eosinophils and LTB4-induced chemotaxis of guinea pig eosinophils were abolished by 1 microM of sulochrin. Finally, sulochrin potently inhibited LTB4-induced infiltration of eosinophils into the skin of guinea-pig in vivo.
CONCLUSIONS:
These results suggest that sulochrin is a potent inhibitor of various effector functions of eosinophils. Sulochrin and its derivatives may be useful in the development of therapeutic approaches for patients with allergic diseases.
AuthorsH Ohashi, Y Motegi, H Kita, G J Gleich, T Miura, M Ishikawa, H Kawai, H Fukamachi
JournalInflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 47 Issue 10 Pg. 409-15 (Oct 1998) ISSN: 1023-3830 [Print] Switzerland
PMID9831326 (Publication Type: Journal Article)
Chemical References
  • Anti-Allergic Agents
  • Benzoates
  • Immunoglobulin A
  • Immunoglobulin G
  • Interleukin-8
  • Platelet Activating Factor
  • Superoxides
  • Leukotriene B4
  • Leukotriene C4
  • sulochrin
  • Sepharose
Topics
  • Animals
  • Anti-Allergic Agents (pharmacology)
  • Benzoates (pharmacology)
  • Cell Degranulation (drug effects)
  • Chemotaxis, Leukocyte (drug effects)
  • Eosinophils (drug effects, immunology, physiology)
  • Guinea Pigs
  • Humans
  • Immunoglobulin A (immunology)
  • Immunoglobulin G (immunology)
  • Interleukin-8 (biosynthesis)
  • Leukotriene B4 (pharmacology)
  • Leukotriene C4 (metabolism)
  • Platelet Activating Factor (pharmacology)
  • Sepharose
  • Superoxides (metabolism)

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