Pushparaj, P. N., Tay, H. K., Wang, C.-C., Hong, W. and Melendez, A. J. (2009) VAMP8 Is Essential in Anaphylatoxin-Induced Degranulation, TNF-alpha Secretion, Peritonitis, and Systemic Inflammation. Journal of Immunology, 183(2), pp. 1413-1418. (doi: 10.4049/jimmunol.0804061)
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Publisher's URL: http://dx.doi.org/10.4049/jimmunol.0804061
Abstract
VAMP8, a member of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) family of fusion proteins, initially characterized in endosomal and endosomal-lysosomal fusion, may also function in regulated exocytosis. VAMP8 physiological function in inflammation has not been elucidated. In this paper, we show that deficiency of VAMP8 protects mice from anaphylatoxin (C5a)-induced neutropenia, peritonitis, and systemic inflammation. We show that, in vivo, VAMP8 deletion inhibits neutropenia and phagocyte recruitment. We also show that in macrophages, VAMP8 localizes on secretory granules and degranulation is inhibited in VAMP8-deficient macrophages. Moreover, VAMP8−/− mice show reduced systemic inflammation with inhibition of serum TNF-α levels, whereas IL-1β, IL-6, and MIP1α release are not affected. In wild-type macrophages, TNF-α colocalizes with VAMP8-positive vesicles, and in VAMP8-deficient macrophages, the TNF-α release is inhibited. Furthermore, VAMP8 regulates the release of TNF-α and β-hexosaminidase triggered by fMLP, and VAMP8−/− mice are protected from fMLP-induced peritonitis. These data demonstrate that the VAMP8 vesicle-associated-SNARE is required for the proper trafficking of secretory lysosomal granules for exocytosis in macrophages and for the release of the potent proinflammatory cytokine, TNF-α.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Tay, Dr Hwee Kee and Pushparaj, Dr Peter |
| Authors: | Pushparaj, P. N., Tay, H. K., Wang, C.-C., Hong, W., and Melendez, A. J. |
| College/School: | College of Medical Veterinary and Life Sciences |
| Journal Name: | Journal of Immunology |
| Journal Abbr.: | J. Immunol. |
| Publisher: | American Association of Immunologists |
| ISSN: | 0022-1767 |
| ISSN (Online): | 1550-6606 |
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