CCR3 gene knockout inhibits proliferation, differentiation, and migration of eosinophils in allergic rhinitis model mice

Allergic rhinitis (AR) is characterized by various bothersome clinical symptoms of the nasal mucosa that impaired the quality of daily life. Different chemokine receptors play a crucial role in the recruitment of inflammatory cells in AR. However, the effect of CC chemokine receptor (CCR) 3 on the function of eosinophils (EOS) is still unclear. We investigated the effect of CCR3 on EOS in a murine model of OVA-mediated allergic rhinitis using CCR3-deficient (CCR3^-/-) mice. In vitro, bone marrow of CCR3^-/- and wild-type (WT) mice were used to investigate the induction and development of EOS. In vivo, Allergic rhinitis was initiated in CCR3^-/- and wild-type (WT) mice by passive transfer OVA, followed by detecting the eosinophil infiltration of the nasal mucosa and bone marrow. Then CD34⁺ progenitor cells in bone marrow and blood were evaluated by IHC analysis. Furthermore, the degranulation proteins of EOS in nasal mucosa, marrow, blood and NALF were determined by IHC, real-time PCR analysis and Western blot. We found that CCR3 gene can regulate the growth and development of primary cultured eosinophils. Knockout CCR3 gene can inhibit the proliferation and degranulation of EOS. The infiltration of eosinophils in the nasal mucosa following OVA-challenged, was significantly higher in WT mice compared with those stimulated with phosphate-buffered saline (PBS) for WT, but that was not seen in similarly treated CCR3^-/- mice. Besides, the number of CD34⁺ progenitor cells in bone marrow and blood were also suppressed in CCR3^-/- mice. The degranulation proteins of EOS expressed in nasal mucosa, marrow, blood and NALF were decreased in CCR3^-/- AR mice compared with WT-AR mice. And the clinical symptoms were significantly alleviated. The expression of granulation proteins in NALF were not detected in both untreated CCR3^-/- mice and WT mice. These results demonstrate a contribution of CCR3 to both the growth, migration, and degranulation of EOS during allergic rhinitis.