thromboxane-b2 and Pulmonary-Eosinophilia

The aim of this study was to examine antigen-induced lung cell migration, eosinophil activation, and pulmonary reactivity of Wistar rats exposed to a new sensitization technique. The animals were sensitized with a single subcutaneous implant of a fragment of heat coagulated hen egg white and challenged 21 days later with an intratracheal injection of heat-aggregated ovalbumin (EWI). For comparison, another group of rats were sensitized by an intraperitoneal injection of ovalbumin in alum as adjuvant, with one booster on day 14 and challenge on day 21 post immunization (OVA/AL). Twenty-four hours after antigen challenge, the EWI group presented a higher number of eosinophils in the bronchoalveolar lavage (BAL) (4.85 +/- 1.43 x 10(6)) than the OVA/AL group (0.2 +/- 0.06 x 10(6)) or the control group, where the level of eosinophils were essentially undetectable. Levels of eosinophil peroxidase activity were increased in the cell-free BAL and homogenates of lung tissue in the EWI group (12.10 +/- 2.97 mg/mL and 36.14 +/- 7.21 ng/mg, respectively), but not in the OVA/AL group (4.83 +/- 1.4 ng/mL and 11.95 +/- 2.54 ng/mg, respectively), as compared with controls (5.16 +/- 1.65 ng/mL and 12.13 +/- 1.74 ng/mg, respectively). Thromboxane B2 levels were also increased in the BAL of EWI group (2.89 +/- 0.54 ng/mL) but not the OVA/AL group (1.13 +/- 0.23 ng/mL) as compared with controls (1.14 +/- 0.19 ng/mL). In contrast, the levels of prostaglandin E2 in the BAL were increased in both groups (456.4 +/- 11.8 pg/mL in the EWI group and 303.5 +/- 31.7 pg/mL in the OVA/AL group) as compared with controls (205.7 +/- 29.7 ng/mL). Moreover, only the EWI group developed increased pulmonary reactivity to serotonin (around two-fold), 24 hours after antigen challenge. The extent of lung eosinophil migration and activation and the pulmonary hyperreactivity induced by this novel sensitization procedure without adjuvants represents a significant improvement over existing experimental models of asthma.

Topics: Animals; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Dinoprostone; Disease Models, Animal; Eosinophil Peroxidase; Eosinophils; Immunization; Ovalbumin; Peroxidases; Pulmonary Eosinophilia; Rats; Rats, Wistar; Respiratory Function Tests; Respiratory Hypersensitivity; Serotonin; Thromboxane B2

To elucidate the mechanism of development of asthma, we tried to develop a model which elicited a late asthmatic response by a combination of systemic and inhaled sensitization with ovalbumin in guinea pigs. Eighty-seven percent of animals elicited both an immediate and late asthmatic response after the third antigen inhalation. Airway eosinophilia and airway hyperresponsiveness (AHR) induced after the third challenge were more severe than those after the first challenge. There was a good correlation between airway eosinophilia and AHR in this model under experimental modulation of the number of eosinophils, such as by interleukin 5 or antieosinophil antibody injection. These results demonstrate that eosinophils play an important role in the development of late asthmatic response and AHR.

Topics: Animals; Antibodies; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Bronchoconstrictor Agents; Disease Models, Animal; Eosinophils; Guinea Pigs; Histamine; Interleukin-5; Leukocyte Count; Leukotriene C4; Male; Methacholine Chloride; Ovalbumin; Passive Cutaneous Anaphylaxis; Pulmonary Eosinophilia; Thromboxane B2; Time Factors