Blocking Mast Cell–Mediated Type I Hypersensitivity in Experimental Allergic Conjunctivitis by Monocyte Chemoattractant Protein-1/CCR2

Tominaga, Takeshi; Miyazaki, Dai; Sasaki, Shin‐ichi; Mihara, Sachiko; Komatsu, Naoki; Yakura, Keiko; Inoue, Yoshitsugu

doi:10.1167/iovs.09-3637

Cited by 26 publications

(17 citation statements)

References 29 publications

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“…A study by Miyazaki et al showed that CCL2 protein was expressed in the conjunctival epithelium of mouse experimental allergic conjunctivitis and CCL2 subconjunctival injection induced mast cell degranulation. 24 Our results are consistent with their findings. They also reported that blocking the CCL2-CCR2 signaling cascade could attenuate signs and symptoms of the acute phase of experimental allergic conjunctivitis.…”

Section: Ccl2 Expression and Degranulation In Mast Cellssupporting

confidence: 93%

“…They also reported that blocking the CCL2-CCR2 signaling cascade could attenuate signs and symptoms of the acute phase of experimental allergic conjunctivitis. 24 Further experiments analyzing RW-induced experimental allergic conjunctivitis using mast cell-deficient mice to clarify mast cell-conjunctival epithelial cell interactions are now ongoing.…”

Section: Ccl2 Expression and Degranulation In Mast Cellsmentioning

confidence: 99%

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Interaction Between Conjunctival Epithelial Cells and Mast Cells Induces CCL2 Expression and Piecemeal Degranulation in Mast Cells

Iwamoto

Asada

Ebihara

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Intraepithelial mast cells are observed in giant papillae tissue samples obtained from patients with atopic keratoconjunctivitis (AKC)/vernal keratoconjunctivitis (VKC). We examined the roles of interaction between the conjunctival epithelial cells and mast cells. METHODS.The interaction between human mast cells and conjunctival epithelial cells (HCjE) was investigated using a coculture model. Protein array analysis, ELISA, and real-time PCR were performed to test the interaction. Tissue samples (n ¼ 6) from giant papillae were resected for therapeutic purposes, and subjected to immunohistological analysis of CCL2 expression. Recombinant CCL2 (10 ng/mL) was reacted with the cultured human mast cells and ultrastructural analysis was performed. A ragweed (RW)-induced mouse experimental allergic conjunctivitis model was used to examine ccl2 mRNA expression and mast cell morphology.RESULTS. Protein array and real-time PCR analyses showed that CCL2 protein/mRNA expression was induced by mast cell-HCjE coculture. Upregulation of CCL2 mRNA was observed in mast cells, whereas in situ CCL2 expression was observed at the conjunctival epithelium of the giant papillae by immunohistochemistry. Ultrastructural analysis showed that recombinant CCL2 treatment induced piecemeal degranulation (PMD) in the mast cells. Ultrastructural analysis of tissues from the giant papillae showed PMD of mast cells within the conjunctival epithelial cells. The RW-induced experimental allergic conjunctivitis model showed increased ccl2 mRNA expression and PMD morphology in the conjunctivae. CONCLUSIONS. Mast cell-conjunctival epithelial cell interaction induces CCL2 expression and subsequent PMD.Keywords: allergy, conjunctivitis, mast cell, degranulation M ast cell activation and migration within and around the conjunctival epithelium is one of the histopathologic features of severe chronic allergic conjunctivitis, atopic keratoconjunctivitis (AKC), 1 and vernal keratoconjunctivitis (VKC).2 In our study, we investigated possible interactions of mast cells and conjunctival epithelial cells using in vitro coculture models, and we found that CCL2 expression in mast cells was upregulated by coculture. A previous report showed that CCL2 could induce piecemeal degranulation (PMD) in basophils.3 PMD and anaphylactic degranulation are known as two distinct types of mast cell degranulation. 4,5 Anaphylactic degranulation is a degranulation style with antecedent granuleto-granule and/or granule-to-plasma membrane fusions. On the other hand, gradual emptying of cytoplasmic secretory granules in the absence of granule-to-granule or granule-to-plasma membrane fusion events is observed in PMD. Previously, we reported that 34 of 168 mast cells observed in the giant papillae of eight eyes obtained from VKC patients showed PMD, whereas only 28 of the 168 mast cells had the morphology of anaphylactic degranulation. 6 These results suggested that not only anaphylactic degranulation, but also PMD might have some roles in the pathophysiology of AKC and VKC....

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Section: Ccl2 Expression and Degranulation In Mast Cellssupporting

confidence: 93%

Section: Ccl2 Expression and Degranulation In Mast Cellsmentioning

confidence: 99%

Interaction Between Conjunctival Epithelial Cells and Mast Cells Induces CCL2 Expression and Piecemeal Degranulation in Mast Cells

Iwamoto

Asada

Ebihara

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…MCP1 is necessary for type I hypersensitivity reaction, such as allergic conjunctivitis, and the blocking of MCP1 prevents allergen from stimulating mast cell degranulation (34). MCP1 expression is under the control of histone modifications (24).…”

Section: Discussionmentioning

confidence: 99%

Histone Deacetylase 3 Mediates Allergic Skin Inflammation by Regulating Expression of MCP1 Protein

Kim¹,

Kim²,

Park³

et al. 2012

Journal of Biological Chemistry

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“…A superfamily of small, structurally related cytokine molecules, chemokines are characterized by their ability to affect trafficking of leukocytes. Some chemokines, such as CCL2/MCP-1 (monocyte chemotactic protein 1), CCL3/MIP-1␣ (macrophage inflammatory protein-1␣), CCL5/RANTES (regulated upon activation, normal T-cell expressed and secreted), and CCL11/eotaxin-1, have been reported to activate mouse, rat, or human mast cells (3)(4)(5)(6). Abundant expression of these CC chemokines and accumulation of leukocytes has also been observed in allergic inflammatory tissues (7)(8)(9).…”

mentioning

confidence: 99%

Evidence That Formation of Vimentin·Mitogen-activated Protein Kinase (MAPK) Complex Mediates Mast Cell Activation following FcεRI/CC Chemokine Receptor 1 Cross-talk

Toda

Kuo

Borman

et al. 2012

Journal of Biological Chemistry

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Background: CC chemokine ligand 2 (CCL2) recruits leukocytes in inflammatory tissues. Results: Vimentin, a cytoskeletal protein, interacted with phosphorylated MAPKs, was critical for CCL2 production in mast cells activated via F⑀cRI and a CC chemokine receptor. Conclusion: Vimentin was involved in optimal CCL2 production in mast cells. Significance: This work contributes to understanding of mechanisms for chemokine production in mast cells, which are therapeutic targets for allergic inflammation.

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Blocking Mast Cell–Mediated Type I Hypersensitivity in Experimental Allergic Conjunctivitis by Monocyte Chemoattractant Protein-1/CCR2

Abstract: Stimulation of the co-stimulatory axis of CCR2 by MCP-1 is essentially required for mast cell-mediated hypersensitivity reactions in mouse eyes.

Cited by 26 publications

References 29 publications

Interaction Between Conjunctival Epithelial Cells and Mast Cells Induces CCL2 Expression and Piecemeal Degranulation in Mast Cells

Interaction Between Conjunctival Epithelial Cells and Mast Cells Induces CCL2 Expression and Piecemeal Degranulation in Mast Cells

Histone Deacetylase 3 Mediates Allergic Skin Inflammation by Regulating Expression of MCP1 Protein

Evidence That Formation of Vimentin·Mitogen-activated Protein Kinase (MAPK) Complex Mediates Mast Cell Activation following FcεRI/CC Chemokine Receptor 1 Cross-talk

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