Possible Physiological Roles of Proteolytic Products of Actin in Neutrophils of Patients with Behcet's Disease.

  • YAMASHITA Shozo
    Department of Biochemistry, Faculty of Pharmaceutical Sciences, Hoshi University Laboratory of Racing Chemistry
  • SUZUKI Akiko
    Department of Biochemistry, Faculty of Pharmaceutical Sciences, Hoshi University
  • KAMADA Masafumi
    Department of Biochemistry, Faculty of Pharmaceutical Sciences, Hoshi University
  • YANAGITA Tamiko
    Department of Internal Medicine, Teikyo University
  • HIROHATA Shunsei
    Department of Internal Medicine, Teikyo University
  • TOYOSHIMA Satoshi
    Department of Biochemistry, Faculty of Pharmaceutical Sciences, Hoshi University

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説明

A truncated actin with an N-terminus of Met-44 is known to be selectively increased in neutrophils of patients with Behçet’s disease and to be generated proteolytically by PMN-elastase (Yamashita S. et al., Biol. Pharm. Bull., 23, 519—522 (2000); Biol. Pharm. Bull., 24, 119—122 (2001)). In this study, the functions of the N-terminal peptide consisting of Asp-2 to Val-43 of β-actin (42-merP) and the truncated actin with an N-terminus of Met-44 were examined. We first confirmed that the 42-merP existed in the patient plasma. The motility of human peripheral blood neutrophils and neutrophilic granulocytes differentiated from HL-60 cells was suppressed by the 42-merP. Furthermore, when neutrophil-like cells from HL-60 cells were preincubated with 10 nM 42-merP, migration of the cells induced by chemotactic factors such as fMLP and IL-8 was suppressed. The release of PMN-elastase, which is a neutrophil granular enzyme that is responsible for the production of the 42-merP and truncated actin, was suppressed by pretreating the neutrophils with 42-merP before fMLP-stimulation. The truncated actin was unable to polymerize in 0.1 M KCl, suggesting that the increase of truncated actin damages the reconstitution capacity of actin in neutrophils of the patients. These results suggest that the increase of 42-merP and truncated actin in patients with Behçet’s disease changes functions of neutrophils

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