Cutting edge: VacA, a vacuolating cytotoxin of Helicobacter pylori, directly activates mast cells for migration and production of proinflammatory cytokines.
Mucosal mast cells strategically located at the optimal site interact with invading bacteria. Presence of VacA, the virulent Helicobacter pylori cytotoxin, is correlated with the severity of H. pylori-induced gastritis. To examine the mechanisms of inflammation in H. pylori-induced gastritis, we administered VacA to the mice. Inoculation of VacA resulted in epithelium vacuolization and marked infiltrations of mast cells and mononuclear cells into the mucosal epithelium within 24 h. In an in vitro study using bone marrow-derived mast cells, VacA directly bound and showed a chemotactic activity to the mast cell. In addition, VacA induced bone marrow-derived mast cells to produce proinflammatory cytokines, TNF-alpha, macrophage-inflammatory protein-1alpha, IL-1beta, IL-6, IL-10, and IL-13 in a dose-dependent manner without causing degranulation. The present study suggests that early activation of mast cells by VacA may be the host early response to clear the bacteria and also may contribute to the pathogenesis of H. pylori-induced gastritis.
Supajatura
Volaluck
V
Department of Dermatology, Juntendo University School of Medicine, Tokyo, Japan.
Ushio
Hiroko
H
Wada
Akihiro
A
Yahiro
Kinnosuke
K
Okumura
Ko
K
Ogawa
Hideoki
H
Hirayama
Toshiya
T
Ra
Chisei
C
D000284:Administration, Oral; D000818:Animals; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology; D002630:Chemotactic Factors / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis*; D003603:Cytotoxins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D005756:Gastritis / Q000276:immunology* / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology / Q000473:pathology; D016480:Helicobacter pylori / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011485:Protein Binding / Q000276:immunology; D014617:Vacuoles / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D001426:Bacterial Proteins; D002630:Chemotactic Factors; D016207:Cytokines; D003603:Cytotoxins; C074689:VacA protein, Helicobacter pylori