CCR3 signaling in Eosinophils

Eosinophils are a key class of leukocytes involved in inflammatory responses, including allergic reactions in skin and airway. The eosinophil response in inflammation is absent in mice lacking CCR3, indicating the key role of this G protein coupled receptor in inflammation and allergic responses. Eotaxin is a chemokine ligand for CCR3 that recruits eosinophils to the site of inflammation and activates them. Other chemokine ligands of CCR3 include eotaxin-2, MCP-3, MCP-4, and RANTES. Multiple signaling pathways activated by CCR3 participate in the inflammatory response of eosinophils. Eotaxin stimulates intracellular calcium release, production of reactive oxygen species, and changes in actin polymerization through a pertussis sensitive pathway. Rho and ROCK regulate actin stress fiber formation and are required for eosinophil chemotaxis. Rho is a G protein that activates ROCK, a protein kinase. Map kinase pathways are also involved in chemotaxis. Another key action of activated eosinophils is the release of reactive oxygen species, causing tissue damage during chronic inflammatory responses. Blocking eosinophil activation and the signaling pathways that lead to chemotaxis, degranulation and reactive oxygen release may alleviate inflammatory conditions and inflammation-associated tissue damage.

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REFERENCES: Boehme, S.A. et al. (1999) Activation of mitogen-activated protein kinase regulates eotaxin-induced eosinophil migration. J. Immunol. 163(3), 1611-8 Elsner, J. et al. (1996) Human eotaxin represents a potent activator of the respiratory burst of human eosinophils. Eur. J. Immunol. (8), 1919-25 Elsner, J. et al. (1998) Eotaxin-2 activates chemotaxis-related events and release of reactive oxygen species via pertussis toxin-sensitive G proteins in human eosinophils. Eur J Immunol 28(7), 2152-8 Kampen, G.T. et al. (2000) Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases. Blood 95(6), 1911-7 Ma, W. et al. (2002) CCR3 is essential for skin eosinophilia and airway hyperresponsiveness in a murine model of allergic skin inflammation. J. Clin. Invest. 109(5), 621-8 Tetsuya Adachi, et al. The Functional Role of Rho and Rho-Associated Coiled-Coil Forming Protein Kinase in Eotaxin Signaling of Eosinophils. The Journal of Immunology, Vol 167, 2001, 4609-4615.