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CD39 is the dominant Langerhans cell associated ecto-NTPDase: Modulatory roles in inflammation and immune responsiveness
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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