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Human β Defensin-3 Increases CD86 Expression on Monocytes by Activating the ATP-Gated Channel P2X7.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2015 Nov 01; Vol. 195 (9), pp. 4438-45. Date of Electronic Publication: 2015 Sep 28. - Publication Year :
- 2015
-
Abstract
- Human β defensin-3 (hBD-3), an epithelial cell-derived antimicrobial peptide, mediates chemotaxis and activation of myeloid cells. In this study, we provide evidence that hBD-3 induces the costimulatory molecule CD86 on primary human monocytes by a mechanism involving autocrine activation of ionotropic P2X7 receptors (P2X7R) by ATP. Incubation of monocytes with hBD-3 resulted in increased expression of both the CD80 and CD86 costimulatory molecules. Treatment of monocytes with a selective P2X7R antagonist inhibited the ability of hBD-3 to induce expression of CD86 but not CD80. The hBD-3-dependent upregulation of CD86 was also attenuated in monocytes incubated with apyrase, a potent scavenger of extracellular ATP. Finally, direct activation of monocyte P2X7R by exogenous ATP mimicked the ability of hBD-3 to induce CD86 expression. These data suggest that hBD-3 induces monocyte activation by both P2X7-dependent (CD86 upregulation) and P2X7-independent (CD80 upregulation) signaling mechanisms and raise the possibility that activation of P2X7R could play an important role in shaping the inflammatory microenvironment in conditions where hBD-3 is highly expressed, such as psoriasis or oral carcinoma.<br /> (Copyright © 2015 by The American Association of Immunologists, Inc.)
- Subjects :
- Apyrase metabolism
Apyrase pharmacology
B7-1 Antigen genetics
B7-1 Antigen metabolism
B7-2 Antigen genetics
Calcium metabolism
Cells, Cultured
Flow Cytometry
Gene Expression drug effects
Humans
Monocytes metabolism
Purinergic P2X Receptor Antagonists pharmacology
Receptors, Purinergic P2X7 genetics
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction drug effects
Signal Transduction genetics
Adenosine Triphosphate pharmacology
B7-2 Antigen metabolism
Monocytes drug effects
Receptors, Purinergic P2X7 metabolism
beta-Defensins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 195
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 26416278
- Full Text :
- https://doi.org/10.4049/jimmunol.1401319