Possible physiological roles of proteolytic products of actin in neutrophils of patients with Behçet's disease.
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 beta-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
Yamashita
S
S
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Suzuki
A
A
Kamada
M
M
Yanagita
T
T
Hirohata
S
S
Toyoshima
S
S
D000199:Actins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019943:Amino Acid Substitution; D001528:Behcet Syndrome / Q000235:genetics / Q000378:metabolism*; D015550:Cell Degranulation / Q000235:genetics; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D016209:Interleukin-8 / Q000494:pharmacology; D019272:Leukocyte Elastase / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000502:physiology
D000199:Actins; D007202:Indicators and Reagents; D016209:Interleukin-8; D010446:Peptide Fragments; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019272:Leukocyte Elastase