Mast cells and basophils, which are activated by IgE and allergens through the high affinity IgE receptor (Fc epsilon RI), play a prominent role in anaphylaxis in the mouse. Mice deficient in this receptor become resistant to passive anaphylaxis. As a first step in developing an in vivo model that more closely mimics the IgE-mediated responses in man, we used a combination of transgenic and embryonic stem cell technology to generate a mouse line in which the murine Fc epsilon RI alpha-chain has been replaced with its human homologue. We demonstrate here that these mice express a tetrameric high affinity IgE receptor, in which the human alpha-chain associates with the murine beta- and gamma-chains, and that upon triggering with relevant Ag, this receptor mediates the initiation of the expected intracellular events. In addition, we show that the human alpha-chain restores an anaphylactic response to the nonresponsive alpha-deficient parental mouse line. This "humanized" mouse represents a potentially important model system, not only for studying the role of IgE in human immune responses, but also for testing potential therapeutic reagents that can interfere with responses mediated through the human Fc epsilon RI receptor.

Anaphylaxis mediated through a humanized high affinity IgE receptor / D. Dombrowicz, A.T. Brini, V. Flamand, E. Hicks, J.N. Snouwaert, J.P. Kinet, B.H. Koller. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 157:4(1996 Aug 15), pp. 1645-1651.

Anaphylaxis mediated through a humanized high affinity IgE receptor

A.T. Brini
Secondo
;
1996

Abstract

Mast cells and basophils, which are activated by IgE and allergens through the high affinity IgE receptor (Fc epsilon RI), play a prominent role in anaphylaxis in the mouse. Mice deficient in this receptor become resistant to passive anaphylaxis. As a first step in developing an in vivo model that more closely mimics the IgE-mediated responses in man, we used a combination of transgenic and embryonic stem cell technology to generate a mouse line in which the murine Fc epsilon RI alpha-chain has been replaced with its human homologue. We demonstrate here that these mice express a tetrameric high affinity IgE receptor, in which the human alpha-chain associates with the murine beta- and gamma-chains, and that upon triggering with relevant Ag, this receptor mediates the initiation of the expected intracellular events. In addition, we show that the human alpha-chain restores an anaphylactic response to the nonresponsive alpha-deficient parental mouse line. This "humanized" mouse represents a potentially important model system, not only for studying the role of IgE in human immune responses, but also for testing potential therapeutic reagents that can interfere with responses mediated through the human Fc epsilon RI receptor.
FC-EPSILON-RI ; EPIDERMAL LANGERHANS CELLS ; IMMUNOGLOBULIN-E ; ALPHA-CHAIN ; EXPRESSION ; GENE ; GENERATION ; ANTIBODY
Settore BIO/14 - Farmacologia
15-ago-1996
Article (author)
File in questo prodotto:
File Dimensione Formato  
Dombrowicz et al - J Imm 1996.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 1.8 MB
Formato Adobe PDF
1.8 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Dombrowicz et al - J Imm 1996.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 1.8 MB
Formato Adobe PDF
1.8 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/198851
Citazioni
  • ???jsp.display-item.citation.pmc??? 51
  • Scopus 92
  • ???jsp.display-item.citation.isi??? 95
social impact