ALLOXAN DIABETES REDUCES PLEURAL MAST-CELL NUMBERS AND THE SUBSEQUENTEOSINOPHIL INFLUX INDUCED BY ALLERGEN IN SENSITIZED RATS

Alloxan damages insulin-producing cells and has been used as an induce r of experimental diabetes in several animal species, In this study, a dministration of alloxan (40 mg/kg, i.v.) to rats was followed by a se lective and time-dependent reduction in the number of pleural mast cel ls (50+/-2.2%, p<0.01; mean +/- SEM), while mononuclear cell and eosin ophil counts were not altered. As compared to naive rats, the reductio n in mast cell numbers was first noted 48 h following alloxan administ ration and remained unaltered for at least 60 days, It is noteworthy, that the depletion in the mast cell population was not accompanied by alterations in the total amount of histamine stored per cell. Sensitiz ed rats turned diabetic by alloxan treatment performed 72 h before cha llenge showed a less pronounced antigen-induced mast cell degranulatio n compared to nondiabetic rats, Moreover, rats injected with alloxan 7 2 and 48 but not 24 h before challenge, reacted to allergenic challeng e with 50% reduction in the number of eosinophils recruited to the ple ural cavity within 24 h. We found that the less pronounced eosinophil accumulation did not relate to an intrinsic cell locomotor abnormality since eosinophils from diabetic rats presented similar chemotactic re sponses to LTB(4) and PAF in vitro as compared to matching controls, I nsulin (3 IU/rat) restored basal levels of mast cells and reversed the subsequent inhibition of allergen-induced pleural eosinophilia, sugge sting a causative relationship between these phenomena. Treatment with insulin also significantly increased the number of mast cells in the pleural cavity of naive rats (from 637+/-57 to 978+/-79x10(3) cells/ca vity, p<0.001), Consistently, previous depletion of mast cells by mean s of local treatment with compound 48/80 significantly reduced the ant igen-induced eosinophil recruitment in sensitized animals, We conclude that the reduction in the pleural mast cell population noted in allox an-treated rats could be directly implicated in the diminished pleural eosinophil influx following allergen challenge. This hyporesponsivene ss is independent of an intrinsic abnormality of cell chemotaxis, but can be imitated by local mast cell depletion.