Interleukin-8 receptor modulates IgE production and B-cell expansion and trafficking in allergen-induced pulmonary inflammation

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Abstract

We examined the role of the interleukin-8 (IL-8) receptor in a murine model of allergen-induced pulmonary inflammation using mice with a targeted deletion of the murine IL-8 receptor homologue (IL-8r–/–). Wild-type (Wt) and IL-8r–/– mice were systemically immunized to ovalbumin (OVA) and were exposed with either single or multiple challenge of aerosolized phosphate-buffered saline (OVA/PBS) or OVA (OVA/OVA). Analysis of cells recovered from bronchoalveolar lavage (BAL) revealed a diminished recruitment of neutrophils to the airway lumen after single challenge in IL-8r–/– mice compared with Wt mice, whereas multiply challenged IL-8r–/– mice had increased B cells and fewer neutrophils compared with Wt mice. Both Wt and IL-8r–/– OVA/OVA mice recruited similar numbers of eosinophils to the BAL fluid and exhibited comparable degrees of pulmonary inflammation histologically. Both total and OVA-specific IgE levels were greater in multiply challenged IL-8r–/– OVA/OVA mice than in Wt mice. Both the IL-8r–/– OVA/OVA and OVA/PBS mice were significantly less responsive to methacholine than their respective Wt groups, but both Wt and IL-8r mice showed similar degrees of enhancement after multiple allergen challenge. The data demonstrate that the IL-8r modulates IgE production, airway responsiveness, and the composition of the cells (B cells and neutrophils) recruited to the airway lumen in response to antigen.

Authors

George T. De Sanctis, James A. MacLean, Shixin Qin, Walter W. Wolyniec, Hartmut Grasemann, Chandri N. Yandava, Aiping Jiao, Thomas Noonan, Joan Stein-Streilein, Francis H.Y. Green, Jeffrey M. Drazen