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| CD39 is the dominant Langerhans cell associated ecto-NTPDase: Modulatory roles in inflammation and immune responsiveness |
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| Author(s): Mizumoto N, Kumamoto T, Robson SC, Sevigny J, Matsue H, Enjyoji K, Takashima A |
| Source: NATURE MEDICINE Volume: 8 Issue: 4 Pages: 358-365 Published: APR 2002 |
| Times Cited: 104 References: 41 |
| Abstract: CD39, the endothelial ecto-nucleoside triphosphate diphosphohydrolase ( NTPDase), regulates vascular inflammation and thrombosis by hydrolyzing ATP and ADP. Although ecto-NTPDase activities have been used as a marker of epidermal dendritic cells ( DCs) known as Langerhans cells, the identity and function of these activities remain unknown. Here we report that Langerhans cells in CD39(-/-) mice express no detectable ecto-NTPDase activity. Irritant chemicals triggered rapid ATP and ADP release from keratinocytes and caused exacerbated skin inflammation in CD39(-/-) mice. Paradoxically, T cell mediated allergic contact hypersensitivity was severely attenuated in CD39(-/-) mice. As to mechanisms, T cells increased pericellular ATP concentrations upon activation, and CD39(-/-) DCs showed ATP unresponsiveness ( secondary to P2-receptor desensitization) and impaired antigen-presenting capacity. Our results show opposing outcomes of CD39 deficiency in irritant versus allergic contact dermatitis, reflecting its diverse roles in regulating extracellular nucleotide-mediated signaling in inflammatory responses to environmental insults and DC T cell communication in antigen presentation. |
| Document Type: Article |
| Language: English |
| Reprint Address: Takashima, A (reprint author), Univ Texas, SW Med Ctr, Dept Dermatol, Dallas, TX 75235 USA |
Addresses:
1. Univ Texas, SW Med Ctr, Dept Dermatol, Dallas, TX 75235 USA 2. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA |
| Publisher: NATURE AMERICA INC, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental |
| IDS Number: 536ML |
| ISSN: 1078-8956 |
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