Cargando…
Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria
Urticarial rash observed in cryopyrin-associated periodic syndrome (CAPS) caused by nucleotide-binding oligomerization domain–leucine-rich repeats containing pyrin domain 3 (NLRP3) mutations is effectively suppressed by anti–interleukin (IL)-1 treatment, suggesting a pathophysiological role of IL-1β...
Autores principales: | , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2009
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715029/ https://www.ncbi.nlm.nih.gov/pubmed/19364881 http://dx.doi.org/10.1084/jem.20082179 |
_version_ | 1782169724395716608 |
---|---|
author | Nakamura, Yuumi Kambe, Naotomo Saito, Megumu Nishikomori, Ryuta Kim, Yun-Gi Murakami, Makoto Núñez, Gabriel Matsue, Hiroyuki |
author_facet | Nakamura, Yuumi Kambe, Naotomo Saito, Megumu Nishikomori, Ryuta Kim, Yun-Gi Murakami, Makoto Núñez, Gabriel Matsue, Hiroyuki |
author_sort | Nakamura, Yuumi |
collection | PubMed |
description | Urticarial rash observed in cryopyrin-associated periodic syndrome (CAPS) caused by nucleotide-binding oligomerization domain–leucine-rich repeats containing pyrin domain 3 (NLRP3) mutations is effectively suppressed by anti–interleukin (IL)-1 treatment, suggesting a pathophysiological role of IL-1β in the skin. However, the cellular mechanisms regulating IL-1β production in the skin of CAPS patients remain unclear. We identified mast cells (MCs) as the main cell population responsible for IL-1β production in the skin of CAPS patients. Unlike normal MCs that required stimulation with proinflammatory stimuli for IL-1β production, resident MCs from CAPS patients constitutively produced IL-1β. Primary MCs expressed inflammasome components and secreted IL-1β via NLRP3 and apoptosis-associated speck-like protein containing a caspase recruitment domain when stimulated with microbial stimuli known to activate caspase-1. Furthermore, MCs expressing disease-associated but not wild-type NLRP3 secreted IL-1β and induced neutrophil migration and vascular leakage, the histological hallmarks of urticarial rash, when transplanted into mouse skin. Our findings implicate MCs as IL-1β producers in the skin and mediators of histamine-independent urticaria through the NLRP3 inflammasome. |
format | Text |
id | pubmed-2715029 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-27150292009-11-11 Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria Nakamura, Yuumi Kambe, Naotomo Saito, Megumu Nishikomori, Ryuta Kim, Yun-Gi Murakami, Makoto Núñez, Gabriel Matsue, Hiroyuki J Exp Med Article Urticarial rash observed in cryopyrin-associated periodic syndrome (CAPS) caused by nucleotide-binding oligomerization domain–leucine-rich repeats containing pyrin domain 3 (NLRP3) mutations is effectively suppressed by anti–interleukin (IL)-1 treatment, suggesting a pathophysiological role of IL-1β in the skin. However, the cellular mechanisms regulating IL-1β production in the skin of CAPS patients remain unclear. We identified mast cells (MCs) as the main cell population responsible for IL-1β production in the skin of CAPS patients. Unlike normal MCs that required stimulation with proinflammatory stimuli for IL-1β production, resident MCs from CAPS patients constitutively produced IL-1β. Primary MCs expressed inflammasome components and secreted IL-1β via NLRP3 and apoptosis-associated speck-like protein containing a caspase recruitment domain when stimulated with microbial stimuli known to activate caspase-1. Furthermore, MCs expressing disease-associated but not wild-type NLRP3 secreted IL-1β and induced neutrophil migration and vascular leakage, the histological hallmarks of urticarial rash, when transplanted into mouse skin. Our findings implicate MCs as IL-1β producers in the skin and mediators of histamine-independent urticaria through the NLRP3 inflammasome. The Rockefeller University Press 2009-05-11 /pmc/articles/PMC2715029/ /pubmed/19364881 http://dx.doi.org/10.1084/jem.20082179 Text en © 2009 Nakamura et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Nakamura, Yuumi Kambe, Naotomo Saito, Megumu Nishikomori, Ryuta Kim, Yun-Gi Murakami, Makoto Núñez, Gabriel Matsue, Hiroyuki Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria |
title | Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria |
title_full | Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria |
title_fullStr | Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria |
title_full_unstemmed | Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria |
title_short | Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria |
title_sort | mast cells mediate neutrophil recruitment and vascular leakage through the nlrp3 inflammasome in histamine-independent urticaria |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715029/ https://www.ncbi.nlm.nih.gov/pubmed/19364881 http://dx.doi.org/10.1084/jem.20082179 |
work_keys_str_mv | AT nakamurayuumi mastcellsmediateneutrophilrecruitmentandvascularleakagethroughthenlrp3inflammasomeinhistamineindependenturticaria AT kambenaotomo mastcellsmediateneutrophilrecruitmentandvascularleakagethroughthenlrp3inflammasomeinhistamineindependenturticaria AT saitomegumu mastcellsmediateneutrophilrecruitmentandvascularleakagethroughthenlrp3inflammasomeinhistamineindependenturticaria AT nishikomoriryuta mastcellsmediateneutrophilrecruitmentandvascularleakagethroughthenlrp3inflammasomeinhistamineindependenturticaria AT kimyungi mastcellsmediateneutrophilrecruitmentandvascularleakagethroughthenlrp3inflammasomeinhistamineindependenturticaria AT murakamimakoto mastcellsmediateneutrophilrecruitmentandvascularleakagethroughthenlrp3inflammasomeinhistamineindependenturticaria AT nunezgabriel mastcellsmediateneutrophilrecruitmentandvascularleakagethroughthenlrp3inflammasomeinhistamineindependenturticaria AT matsuehiroyuki mastcellsmediateneutrophilrecruitmentandvascularleakagethroughthenlrp3inflammasomeinhistamineindependenturticaria |