Critical role of IgE-dependent mast cell activation in a murine model of allergic conjunctivitis

Ken Fukuda, Masaharu Ohbayashi, Kei Morohoshi, Lane Zhang, Fu-Tong Liu, Santa J. Ono

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: Allergic conjunctivitis is characterized by allergen-specific IgE in the serum and infiltration of eosinophils into the conjunctiva. The role of IgE and mast cells in allergic conjunctivitis is largely unknown, however. Objectives: We investigated the importance of conjunctival mast cells in a murine model of IgE-mediated allergic conjunctivitis. Methods: IgE-mediated allergic conjunctivitis was initiated in C57BL/6-Kit+/+ wild-type mice, mast cell-deficient KitW-sh/W-sh mice, and KitW-sh/W-sh mice that had been subconjunctivally or systemically engrafted with bone marrow-derived, cultured mast cells (BMCMCs) from Kit+/+ wild-type mice, and clinical symptoms and infiltration of eosinophil of the eyes were evaluated. Total numbers of mast cells in the conjunctiva were counted, and the phenotypes of these cells were characterized by means of immunostaining and PCR analysis of murine mast cell proteases. Results: No mast cells were detected in the conjunctiva or eyelid dermis of adult KitW-sh/W-sh mice. Subconjunctival injection of BMCMCs resulted in local mast cell reconstitution, with the numbers of reconstituted mast cells in the conjunctiva and eyelid dermis comparable with those observed in wild-type Kit+/+ littermates. Reconstituted and naive conjunctival mast cells expressed proteases ascribed to connective tissue-type mast cells but not mucosal mast cells. Passive transfer of ragweed-specific IgE followed by antigen challenge resulted in both early-phase clinical symptoms and late-phase eosinophilic inflammation in Kit+/+ mice. These responses, which were significantly decreased in KitW-sh/W-sh mice, were restored on reconstitution of the conjunctival mast cell population. Conclusions: These results suggest a direct contribution of IgE-activated mast cells to both the early-phase reaction and late-phase inflammation during ocular allergy.

Original languageEnglish (US)
JournalJournal of Allergy and Clinical Immunology
Volume124
Issue number4
DOIs
StatePublished - Oct 2009

Fingerprint

Allergic Conjunctivitis
Mast Cells
Immunoglobulin E
Conjunctiva
Eyelids
Dermis
Eosinophils
Cultured Cells
Peptide Hydrolases
Bone Marrow
Inflammation
Ambrosia
Connective Tissue Cells

Keywords

  • adoptive transfer
  • bone marrow-derived mast cells
  • eosinophil
  • IgE
  • inflammation
  • mast cell-deficient mouse
  • mast cells
  • Ocular allergy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Medicine(all)

Cite this

Critical role of IgE-dependent mast cell activation in a murine model of allergic conjunctivitis. / Fukuda, Ken; Ohbayashi, Masaharu; Morohoshi, Kei; Zhang, Lane; Liu, Fu-Tong; Ono, Santa J.

In: Journal of Allergy and Clinical Immunology, Vol. 124, No. 4, 10.2009.

Research output: Contribution to journalArticle

Fukuda, Ken ; Ohbayashi, Masaharu ; Morohoshi, Kei ; Zhang, Lane ; Liu, Fu-Tong ; Ono, Santa J. / Critical role of IgE-dependent mast cell activation in a murine model of allergic conjunctivitis. In: Journal of Allergy and Clinical Immunology. 2009 ; Vol. 124, No. 4.
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abstract = "Background: Allergic conjunctivitis is characterized by allergen-specific IgE in the serum and infiltration of eosinophils into the conjunctiva. The role of IgE and mast cells in allergic conjunctivitis is largely unknown, however. Objectives: We investigated the importance of conjunctival mast cells in a murine model of IgE-mediated allergic conjunctivitis. Methods: IgE-mediated allergic conjunctivitis was initiated in C57BL/6-Kit+/+ wild-type mice, mast cell-deficient KitW-sh/W-sh mice, and KitW-sh/W-sh mice that had been subconjunctivally or systemically engrafted with bone marrow-derived, cultured mast cells (BMCMCs) from Kit+/+ wild-type mice, and clinical symptoms and infiltration of eosinophil of the eyes were evaluated. Total numbers of mast cells in the conjunctiva were counted, and the phenotypes of these cells were characterized by means of immunostaining and PCR analysis of murine mast cell proteases. Results: No mast cells were detected in the conjunctiva or eyelid dermis of adult KitW-sh/W-sh mice. Subconjunctival injection of BMCMCs resulted in local mast cell reconstitution, with the numbers of reconstituted mast cells in the conjunctiva and eyelid dermis comparable with those observed in wild-type Kit+/+ littermates. Reconstituted and naive conjunctival mast cells expressed proteases ascribed to connective tissue-type mast cells but not mucosal mast cells. Passive transfer of ragweed-specific IgE followed by antigen challenge resulted in both early-phase clinical symptoms and late-phase eosinophilic inflammation in Kit+/+ mice. These responses, which were significantly decreased in KitW-sh/W-sh mice, were restored on reconstitution of the conjunctival mast cell population. Conclusions: These results suggest a direct contribution of IgE-activated mast cells to both the early-phase reaction and late-phase inflammation during ocular allergy.",
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AU - Fukuda, Ken

AU - Ohbayashi, Masaharu

AU - Morohoshi, Kei

AU - Zhang, Lane

AU - Liu, Fu-Tong

AU - Ono, Santa J.

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AB - Background: Allergic conjunctivitis is characterized by allergen-specific IgE in the serum and infiltration of eosinophils into the conjunctiva. The role of IgE and mast cells in allergic conjunctivitis is largely unknown, however. Objectives: We investigated the importance of conjunctival mast cells in a murine model of IgE-mediated allergic conjunctivitis. Methods: IgE-mediated allergic conjunctivitis was initiated in C57BL/6-Kit+/+ wild-type mice, mast cell-deficient KitW-sh/W-sh mice, and KitW-sh/W-sh mice that had been subconjunctivally or systemically engrafted with bone marrow-derived, cultured mast cells (BMCMCs) from Kit+/+ wild-type mice, and clinical symptoms and infiltration of eosinophil of the eyes were evaluated. Total numbers of mast cells in the conjunctiva were counted, and the phenotypes of these cells were characterized by means of immunostaining and PCR analysis of murine mast cell proteases. Results: No mast cells were detected in the conjunctiva or eyelid dermis of adult KitW-sh/W-sh mice. Subconjunctival injection of BMCMCs resulted in local mast cell reconstitution, with the numbers of reconstituted mast cells in the conjunctiva and eyelid dermis comparable with those observed in wild-type Kit+/+ littermates. Reconstituted and naive conjunctival mast cells expressed proteases ascribed to connective tissue-type mast cells but not mucosal mast cells. Passive transfer of ragweed-specific IgE followed by antigen challenge resulted in both early-phase clinical symptoms and late-phase eosinophilic inflammation in Kit+/+ mice. These responses, which were significantly decreased in KitW-sh/W-sh mice, were restored on reconstitution of the conjunctival mast cell population. Conclusions: These results suggest a direct contribution of IgE-activated mast cells to both the early-phase reaction and late-phase inflammation during ocular allergy.

KW - adoptive transfer

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KW - inflammation

KW - mast cell-deficient mouse

KW - mast cells

KW - Ocular allergy

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