Role of CCL7 in Type I Hypersensitivity Reactions in Murine Experimental Allergic Conjunctivitis

• Published in: The Journal of immunology (1950) Vol. 198; no. 2; pp. 645 - 656
• Main Authors: Kuo, Chuan-Hui, Collins, Andrea M, Boettner, Douglas R, Yang, YanFen, Ono, Santa J
• Format: Journal Article
• Language: English
• Published: United States American Association of Immunologists 15.01.2017; AAI
• Subjects: Allergy and Other Hypersensitivities; Anaphylaxis; Animal models; Animals; Blotting, Western; Bone marrow; Calcium; Calcium influx; CC chemokine receptors; CCR1 protein; Cell activation; Cell Degranulation - immunology; Chemokine CCL7 - immunology; Chemotaxis; Conjunctiva; Conjunctivitis; Conjunctivitis, Allergic - immunology; Degranulation; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Hay fever; Hypersensitivity; Immunoglobulin E; Mast cells; Mast Cells - immunology; Medical treatment; Mice; Mice, Inbred C57BL; Mice, Knockout; Real-Time Polymerase Chain Reaction; Rodents
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1502416

Molecules that are necessary for ocular hypersensitivity reactions include the receptors CCR1 and CCR3; CCL7 is a ligand for these receptors. Therefore, we explored the role of CCL7 in mast cell activity and motility in vitro and investigated the requirement for CCL7 in a murine model of IgE-mediated allergic conjunctivitis. For mast cells treated with IgE and Ag, the presence of CCL7 synergistically enhanced degranulation and calcium influx. CCL7 also induced chemotaxis in mast cells. CCL7-deficient bone marrow-derived mast cells showed decreased degranulation following IgE and Ag treatment compared with wild-type bone marrow-derived mast cells, but there was no difference in degranulation when cells were activated via an IgE-independent pathway. In vivo, CCL7 was upregulated in conjunctival tissue during an OVA-induced allergic response. Notably, the early-phase clinical symptoms in the conjunctiva after OVA challenge were significantly higher in OVA-sensitized wild-type mice than in control challenged wild-type mice; the increase was suppressed in CCL7-deficient mice. In the OVA-induced allergic response, the numbers of conjunctival mast cells were lower in CCL7-deficient mice than in wild-type mice. Our results demonstrate that CCL7 is required for maximal OVA-induced ocular anaphylaxis, mast cell recruitment in vivo, and maximal FcεRI-mediated mast cell activation in vitro. A better understanding of the role of CCL7 in mediating ocular hypersensitivity reactions will provide insights into mast cell function and novel treatments for allergic ocular diseases.