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.

Hypoxia inducible factor 1α in vascular smooth muscle cells promotes angiotensin II-induced vascular remodeling via activation of CCL7-mediated macrophage recruitment

“…CCL7, also called MCP-3, is an agonist for CCR2 in vivo. It was demonstrated that CCL7 is critical for monocyte mobilization from bone marrow and recruitment to inflammatory sites, since the number of inflammatory monocytes was profoundly reduced in Ccl7 −/− mice 31 . Several studies suggest that CCL7 may also be involved in vascular pathologies 32,33 .…”

Non‐IgE mediated mast cell activation

“…The MC expression profile largely depends on the type of MC examined: progenitor cells vs mature MCs or MC subtypes. Besides inducing bona fide MC chemotactic responses, chemokine receptors have also been implicated in the cross‐talk with other receptors synergistically enhancing FcεRI‐mediated responses such as reported for CCL7 . An excellent review on these receptors was recently published …”

“…In hancing FcεRI-mediated responses such as reported for CCL7. 193 An excellent review on these receptors was recently published. 194 Another interesting receptor that can be mentioned is the ADGRE2 GBCR, a GPCR composed of an Extracellular N-terminal α subunit with 5 epidermal growth factor (EGF)-like adhesion domains binding dermatan sulfate in the skin and a β subunit containing the classical 7-transmembrane domains.…”

Changing the threshold—Signals and mechanisms of mast cell priming

“…CCR1 is expressed by conjunctival mast cells, and subconjunctival injection of CCL3 increased conjunctival mast cell number and degranulation in vivo . Chemokine CCL7, which interacts with CCR1 and CCR3 receptors is upregulated in conjunctival tissue during an OVA‐induced allergic response, and co‐stimulation of FcεRI with CCL7 led to enhanced degranulation …”

“…41 Chemokine CCL7, which interacts with CCR1 and CCR3 receptors is upregulated in conjunctival tissue during an OVA-induced allergic response, and co-stimulation of FcεRI with CCL7 led to enhanced degranulation. 133…”