ALLERGIC EOSINOPHIL-RICH INFLAMMATION DEVELOPS IN LUNGS AND AIRWAYS OF B-CELL-DEFICIENT MICE

Immunoglobulins (Ig), particularly IgE, are believed to be crucially i nvolved in the pathogenesis of asthma and, equally, in allergic models of the disease. To validate this paradigm we examined homozygous muta nt C57BL/6 mice, which are B cell deficient, lacking all Ig. Mice were immunized intraperitoneally with 10 mu g ovalbumin (OVA) plus alum, f ollowed by daily (day 14-20) 30 min exposures to OVA aerosol (OVA/OVA group). Three control groups were run: OVA intraperitoneally plus sali ne (SAL) aerosol (OVA/SAL group); saline intraperitoneally plus saline aerosol; saline intraperitoneally plus OVA aerosol (n = 6-7). Lung an d large airway tissues obtained 24 h after the last OVA or SAL exposur e were examined by light microscopy and transmission electron microsco py (TEM). The Ig-deficient mice receiving OVA/OVA treatment had swolle n and discolored lungs and exhibited marked eosinophilia both in large airway subepithelial tissue (49.2 +/- 12.0 cells/mm basement membrane [BM] versus OVA/SAL control 1.2 +/- 0.3 cells/mm BM; P < 0.001), and perivascularly and peribronchially in the lung (49.3 +/- 9.0 cells/uni t area versus OVA/SAL control 2.6 +/- 0.6 cells/unit area; P < 0.001). The eosinophilia extended to the regional lymph nodes. TEM confirmed the subepithelial and perivascular localization of eosinophils. Mucus cells in large airway epithelium increased from 1.5 +/- 0.8 (OVA/SAL m ice) to 39.5 +/- 5.7 cells/mm BM in OVA/OVA treated mice (P < 0.001). OVA/SAL mice never differed from the other control groups. Correspondi ng experiments in wild-type mice (n = 6-7 in each group) showed qualit atively similar but less pronounced eosinophil and mucus cell changes. Macrophages and CD4(+) T cells increased in lungs of all OVA/OVA trea ted mice. Mast cell number did not differ but degranulation was detect ed only in OVA/OVA-treated wild-type mice. Immunization to OVA followe d by OVA challenges thus cause eosinophil-rich inflammation in airways and lungs of mice without involvement of B cells and Ig.