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http://purl.uniprot.org/citations/17208591http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17208591http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17208591http://www.w3.org/2000/01/rdf-schema#comment"

Background

The calcium-binding protein S100A12 might provoke inflammation and monocyte recruitment through the receptor for advanced glycation end products.

Objective

Because inflammation elicited by S100A12 in vivo had characteristics of mast cell (MC) activation, we aimed to define the mechanism.

Methods

Various MC populations were used to test S100A12 activation assessed on the basis of morphology, histamine release, leukotriene production, and cytokine induction. MC dependence of S100A12-provoked inflammation was tested in mice and on the rat microcirculation by means of intravital microscopy. Immunohistochemistry localized S100A12 in the asthmatic lung, and levels in sputum from asthmatic patients were quantitated by means of ELISA. Expression of the receptor for advanced glycation end products was evaluated by means of RT-PCR and Western blotting.

Results

S100A12 provoked degranulation of mucosal and tissue MCs in vitro and in vivo and amplified IgE-mediated responses. It induced a cytokine profile indicating a role in innate/T(H)1-mediated responses. S100A12-induced edema and leukocyte rolling, adhesion, and transmigration in the microcirculation were MC dependent. Eosinophils in airway tissue from asthmatic patients were S100A12 positive, and levels were increased in sputum. S100A12 responses were partially blocked by an antagonist to the receptor for advanced glycation end products, but MCs did not express mRNA or protein, suggesting an alternate receptor.

Conclusion

This novel pathway highlights the potential importance of S100A12 in allergic responses and in infectious and chronic inflammatory diseases.

Clinical implications

MC activation by S100A12 might exacerbate allergic inflammation and asthma. S100A12 might provide a novel marker for eosinophilic asthma."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.org/dc/terms/identifier"doi:10.1016/j.jaci.2006.08.021"xsd:string
http://purl.uniprot.org/citations/17208591http://purl.org/dc/terms/identifier"doi:10.1016/j.jaci.2006.08.021"xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Alewood P.F."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Alewood P.F."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Yang Z."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Yang Z."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Wang H.W."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Wang H.W."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Cai H."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Cai H."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Yan W.X."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Yan W.X."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Hunt J."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Hunt J."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Hughes J.M."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Hughes J.M."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Hart P."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Hart P."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Armishaw C."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Armishaw C."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Simpson J.L."xsd:string
http://purl.uniprot.org/citations/17208591http://purl.uniprot.org/core/author"Simpson J.L."xsd:string
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