CCR3-Blocking Antibody Inhibits Allergen-Induced Eosinophil Recruitment in Human Skin Xenografts from Allergic Patients View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2002-07-01

AUTHORS

Stéphanie Sénéchal, Olivier Fahy, Thibaut Gentina, Han Vorng, Monique Capron, Andrew F Walls, Alan R McEuen, Mark G Buckley, Qutayba Hamid, Benoît Wallaert, André Bernard Tonnel, Anne Tsicopoulos

ABSTRACT

Eosinophil, basophil, and T helper 2 (TH2) cell recruitment into tissues is a characteristic feature of allergic diseases. These cells have in common the expression of the chemokine receptor CCR3, which may represent a specific pathway for their accumulation in vivo. Although animal models of allergic reactions are available, findings cannot always be extrapolated to man. To overcome these limitations, we have developed a humanized mouse model of allergic cutaneous reaction using severe combined immunodeficiency mice engrafted with skin and autologous peripheral blood mononuclear cells from allergic donors. Intradermal injection of the relevant allergen into human skin xenografts from allergic individuals induced a significant recruitment of human CD4+ T cells, basophils, and TH2-type cytokine mRNA-expressing cells, as well as murine eosinophils. Human skin xenografts, atopic status, and autologous peripheral blood mononuclear cell reconstitution were all mandatory to induce the allergic reaction. Next, we addressed the role of CCR3 in the endogenous mechanisms involved in the inflammatory cell recruitment in this experimental model of allergic cutaneous reaction. In vivo administration of an anti-human CCR3-blocking antibody selectively reduced accumulation of eosinophils but not that of CD4+ cells, basophils, or cells expressing mRNA for TH2-type cytokines. These findings establish a new in vivo model of humanized allergic reaction and suggest that eosinophil migration is mediated mainly through CCR3. Finally, these results suggest that this model might be useful to test human-specific antiallergic modulators. More... »

PAGES

929-939

Identifiers

URI

http://scigraph.springernature.com/pub.10.1097/01.lab.0000020417.13757.05

DOI

http://dx.doi.org/10.1097/01.lab.0000020417.13757.05

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1053423491

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12118095


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94 murine eosinophils
95 pathway
96 patients
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98 peripheral blood mononuclear cells
99 reaction
100 receptor CCR3
101 reconstitution
102 recruitment
103 relevant allergens
104 results
105 role
106 role of CCR3
107 significant recruitment
108 skin
109 skin xenografts
110 specific pathways
111 status
112 tissue
113 vivo
114 vivo administration
115 vivo model
116 xenografts
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