title: Role of CCL7 in Type I Hypersensitivity Reactions in Murine Experimental Allergic Conjunctivitis.
abstract: 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.
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital, Medical Center, Cincinnati, OH 45229; and.
authors.forename: Chuan-Hui
authors.initials: CH
authors.lastname: Kuo
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital, Medical Center, Cincinnati, OH 45229; and.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Collins
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital, Medical Center, Cincinnati, OH 45229; and.
authors.forename: Douglas R
authors.identifier: 0000-0002-0591-443X
authors.initials: DR
authors.lastname: Boettner
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital, Medical Center, Cincinnati, OH 45229; and.
authors.forename: YanFen
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital, Medical Center, Cincinnati, OH 45229; and sjo@ubc.ca.|University of Cincinnati, Cincinnati, OH 45229.
authors.forename: Santa J
authors.initials: SJ
authors.lastname: Ono
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015550:Cell Degranulation / Q000276:immunology; D054410:Chemokine CCL7 / Q000276:immunology*; D003233:Conjunctivitis, Allergic / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C515451:Ccl7 protein, mouse; D054410:Chemokine CCL7