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T. Nakamura, M. Toda, D. Miyazaki, M.E. Rothenberg, S.J. Ono; Eotaxin-1 Drives Terminal Differentiation of Conjunctival Mast Cells . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3753.
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Purpose: Eotaxin-1 is a member of the C-C chemokine subfamily that is expressed in a wide variety of mesenchymal cells and plays an important role in the late phase reaction as an eosinophil chemoattractant. We have previously reported that eotaxin-1 is also essential for the acute phase reaction in the conjunctiva, based upon analyses of eotaxin-1-deficient mice. We report here that eotaxin-1 serves to prime and drive terminal differentiation of mast cells in the conjunctiva. Methods and Results: Passive IgE-sensitization experiments using conjunctival mast cells from eotaxin-1-deficient mice has revealed that addition of recombinant eotaxin-1 rescues the impaired mast cell degranulation observed in these mice, while having no effect on conjunctival mast cells from wild-type mice. These data demonstrate that eotaxin-1 can prime conjunctival mast cells to respond to FceRI cross-linking in a remarkably rapid fashion. The evidence that this priming involves terminal differentiation of the mast cells comes from our finding that eotaxin-1-deficient mice exhibited decreased mRNA expression of mouse mast cell proteases -5 and -6 in the conjunctiva compared with those from wild-type mice. Conclusions: Our current work aims to decipher CCR3-mdeiated signal transduction pathways which modulate expression of mast cell proteases during terminal differentiation. We hope that these experiments will provide a molecular basis for the role eotaxin-1 plays in mast cell development and function.
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