2206 Role of the CC−Chemokine Receptor CCR9 In the Regulation of Inflammatory Process During Allergic Airway Inflammation

Monday, 5 December 2011: 13:45 - 14:00
Xcaret (Cancún Center)

Cynthia López-Pacheco, MD , Immunology, Biomedical Research Institute, UNAM, Mexico City, Mexico

Gisela Du Pont , Immunology, Biomedical Research Institute, UNAM, Mexico City, Mexico

Marc-André Wurbel, PhD , Children's Hospital Boston, Harvard Medical School, Boston, MA

Teresa Fortoul, PhD , Cell and Tissue Biology, School of Medicine, UNAM, Mexico City, Mexico

Gloria Soldevila, PhD , Immunology, Biomedical Research Institute, UNAM, Mexico City, Mexico

Eduardo García-Zepeda, PhD , Immunology, Biomedical Research Institute, UNAM, Mexico City, Mexico

Background: Airway eosinophilia and Th2 lymphocytes-recruitment to the lung are one of the main pathological features of asthma. It is clear now that the axis chemokine/chemokine receptors have a role in controlling leukocyte recruitment and development of the inflammatory process observed in asthma. Although it has been reported that CCR9 receptor is expressed in asthmatic patients, it is not known whether CCR9 may have a regulatory role of the development of this disease.

Our aim was to analyze the expression of CCR9 in a murine model of allergic airway inflammation (WT) and compared to CCR9 deficient (KO) mice.

Methods: Four groups of 6-8 weeks female CCR9-deficient mice were sensitized by intraperitoneal injections of 10 micrograms of ovalbumin (OVA) in alum (ALOH3) diluted in PBS, on days 1 and 8 of the established sensitization protocol. Aerosolised OVA was administered (1% in PBS) on days 15,20 and 34. 24 h after last OVA exposure, mice were sacrificed and bronchoalveolar lavage (BAL) fluid and cells were obtained. Total and differential cell numbers were obtained and characterized cell subpopulations by FACS analysis. Cytokine/chemokine levels were quantified by ELISA and qRT-PCR respectively.

Results: Total cell numbers in BAL were no significantly different between WT and KO mice. Interestingly, reduction in the numbers of eosinophils was observed in CCR9 KO mice compared to WT mice. Histological analysis of lung tissue demonstrated a reduction in the granulocytic population (eosinophils) in CCR9 KO mice. Analysis of cell subpopulations by FACS demonstrated that CD4+ lymphocytes were significantly reduced but CD8+ and CD19+ lymphocytes numbers were not different between WT and CCR9-deficient mice. A population of CCR9+ Gr1+ was altered in KO mice and it correlated with cytological analysis. Furthermore, histological analysis demonstrated alteration in mucus production in allergic airway in CCR9 deficient mice, accompanied with a no-significant reduction of OVA-specific anti-IgE antibodies in serum at the time of analysis.

Conclusions: Altogether, these results suggest that CCR9 may be involved in recruitment of granulocytic cell subpopulation into the allergic airways and have an impact in the regulation of the chronic inflammatory process