Adoptive Transfer of Mast Cells Abolishes the Inflammatory Refractoriness to Allergen in Diabetic Rats

Abstract

Mast cells are pivotal secretory cells primarily implicated in allergen-evoked inflammatory responses and are downregulated following experimental chemical diabetes. Here we tested the hypothesis that a decrease in the number and reactivity of mast cells would account for the hyporesponsiveness of diabetic rats to allergen-induced inflammation. We found that the anaphylactic release of histamine from sensitized ileum, trachea and skin tissues was clearly reduced in rats turned diabetic via intravenous administration of alloxan. Likewise, actively and passively sensitized diabetic rats mounted a weaker allergen-evoked pleural mast cell degranulation and protein extravasation, as compared to sensitized nondiabetic animals, which paralleled a marked reduction in the mast cell population in the pleural cavity. The number of mast cells enumerated in the mesentery from diabetic rats was also clearly reduced. The allergen-evoked plasma leakage in diabetic rats was restored by the transfer of mast cells from sensitized nondiabetic rats. Moreover, the adoptive transfer of sensitized mast cells from diabetics to naive animals led to a lower allergen-induced exudation as compared to the response noted after the transfer of sensitized naive mast cells. Purified mast cells from diabetic rats were hyporesponsive to antigen and compound 48/80 stimulation in vitro as attested by histamine release. Thus, our results show that the phenomenon of refractoriness of diabetic animals to allergen challenge appears to be accounted for by a reduction in the number and reactivity of mast cells.

Mast cell changes in experimental diabetes: focus on attenuation of allergic events

“…Moreover, in the case of diabetic animals fragments of trachea, skin, and intestine showed refractoriness to the antigen challenge in vitro (de Oliveira Barreto et al 2003), providing evidence that similarly to what was noted in the case of free mast cells, those located in tissues seemed to be negatively regulated in diabetes. In addition, the diabetic state was also shown to affect the sensitization stage of the anaphylactic reaction, since the augmentation in total and ovalbumin specific serum IgE levels was suppressed in diabetic sensitized rats .…”

“…The less pronounced eosinophil accumulation did not relate to an intrinsic cell locomotor abnormality since eosinophils from diabetic rats presented similar chemotactic responses in vitro as compared to matching controls (Diaz et al 1996). Moreover, antigen-induced protein leakage (de Oliveira Barreto et al 2003) as well as neutrophil infiltration (unpublished data) were also clearly suppressed in diabetic sensitized rats. Interestingly, we showed that suppression of allergic responses in diabetic rats well correlated with a selective and time-dependent reduction in the number of pleural mast cells (50% ± 2.2%, p < 0.01; mean ± SEM), while other leucocytes were not altered.…”

“…As compared to naive animals, the reduction in mast cell numbers was first noted 48 h following alloxan administration and remained unaltered for at least 60 days (Diaz et al 1996). Furthermore, the amount of histamine stored in diabetic mast cell granules was not different from that found in controls, clearly indicating that alloxan induced a decrease in the number of mast cells rather than their degranulation (Diaz et al 1996, de Oliveira Barreto et al 2003. Altogether these findings suggested that down-regulation of mast cells could be responsible for at least part of refractoriness of diabetic animals to antigen challenge.…”

“…Since mast cells played a critical role not only in eosinophil recruitment but also in other key features of the allergic inflammatory response , we further evaluated how diabetes-associated mast cell disturbance could effect the suppression of allergen-mediated inflammation under diabetic conditions. The reconstitution of the pleural mast cell population in diabetic animals, by means of adoptive transfer system, restored the antigen-induced plasma leakage (de Oliveira Barreto et al 2003). Additionally, the transfer of diabetic sensitized mast cells to normal animals caused a lower pleural exudatory response compared to the response produced by nondiabetic mast cells, indicating that not only the number of mast cells and also their reactivity were significantly reduced in experimental diabetes.…”

“…Additionally, the transfer of diabetic sensitized mast cells to normal animals caused a lower pleural exudatory response compared to the response produced by nondiabetic mast cells, indicating that not only the number of mast cells and also their reactivity were significantly reduced in experimental diabetes. In fact, purified mast cells from diabetic rats were hyporesponssive to antigen and compound 48/80 stimulation in vitro as attested by histamine release (de Oliveira Barreto et al 2003), in direct correlation with increase in the intracellular levels of cAMP (Barreto et al 2004). This was an indicative that augmentation in the amount of cAMP nucleotide could be accounted for by the refractoriness of mast cells under diabetic conditions.…”