ChemR23 Over-expression Modulates Leukocyte Recruitment in vivo

To investigate the role of ChemR23, a receptor for chemerin and resolvin E1, in leukocyte recruitment and inflammatory response.

Methods: The full-length human ChemR23 cDNA was cloned downstream of the human CD11b promoter and the resulting construct was used to generate transgenic mice. Four founder lines were assessed for transgene copy number using real-time PCR. HChemR23 transgenic mice and wide-type control mice were injected intraperitoneally with 1mL zymosan A (1mg/ml) and sacrificed 14 hours later for abdominal lavage and leukocyte collection. Cells were stained with PE-conjugated anti-mouse F4/80 antibody, PE-conjugated anti-human ChemR23 antibody and FITC-conjugated anti-mouse Ly6G antibody and analyzed with flow cytometry.

Results: Four out of eight potential founders were F1 positive hChemR23 transgenic mice based on PCR. One founder carries approximately 64 copies of the transgene and the other three has about 32 copies as estimated with real-time PCR. All the positive founders and their offspring appear healthy and fertile. Following overnight induction of peritoneal inflammation using zymosan A, hChemR23 are detected on the monocytes/macrophages in male transgenic mice. And the transgenic mice recruit fewer macrophages (22% less than wide-type control mice) and slightly fewer granulocytes into the peritoneum compared to wide-type littermates.

Conclusion: HChemR23 over-expressing mice are viable and fertile. ChemR23 and its ligands, chemerin and resolving E1 may play regulatory roles in leukocyte trafficking during acute inflammation.