Role of eosinophils and cell adhesion molecules in the asthmatic response to allergen

Abstract

To evaluate the eosinophil infiltration in lung tissues in asthmatic responses of Brown-Norway rats and guinea pigs, both of which were sensitized with ovalbumin (OA), the time course of changes in respiratory impedance (Zrs) and eosinophil influx after aerosol challenge with OA were measured. The effect of treatment with monoclonal antibody (MoAb) 1A29 against rat intercellular adhesion molecule-1 (ICAM-1) alone and a mixture of MoAb 1A29 and MoAb WT-3 against rat CD18 on asthmatic responses of the rats was studied. Finally, these expressions in lung tissues of the rats were recognized. The number of eosinophils in the subepithelial area was counted in sections of lung tissue stained with Giemsa's solution, using an Interaktive Build-Analyse System (IBAS). All of the rats and 80% of the guinea pigs developed an increase in Zrs 6-7 hours after challenge, indicating that these animals showed a late asthmatic response (LAR). The rats and the guinea pigs with a LAR had higher eosinophil counts than those with an immediate asthmatic response and sensitized, non-challenged animals (p < 0.01). The rats treated with MoAb 1A29 alone (n = 5) and a mixture of MoAb 1A29 and MoAb WT-3 (n = 8) developed significantly smaller increases in Zrs and a smaller eosinophil influx than the control animals treated with phosphate buffered saline (n = 15): 147.3 +/- 3.5, 134.8 +/- 11.6 versus 158.8 +/- 6.3% of baseline; 734 +/- 21, 545 +/- 108 versus 1006 +/- 147 cells/mm2 (p < 0.01). Immunoperoxidase staining of rat lung tissues using MoAb 1A29 or MoAb WT-3 was performed ICAM-1 immunoreactivity was positive in the basilar portion of the epithelium, in the vascular endothelium of the trachea and in the pulmonary vascular endothelium. ICAM-1 immunoreactivity was revealed to be upregulated after challenge. The number of CD18-positive cells in the trachea and in the subepithelial area increased after challenge. These results show that eosinophil infiltration corresponds closely to bronchoconstriction in LAR and that treatment with MoAbs to ICAM-1 and CD18 may be effective in reducing asthmatic symptoms.