Accumulation of tissue macrophages and depletion of resident macrophages in the diabetic thymus in response to hyperglycemia-induced thymocyte apoptosis

Abstract

AimsWe investigated the dynamics and morphology of thymus macrophages in response to thymus involution caused by hyperglycemia. Thymus is an organ affected early and dramatically after the onset of diabetes, losing most of the thymocyte populations but diabetes's impact on the components of the thymus stroma is largely unknown. MethodsRats were injected with streptozotocin and thymus weight, body weight, and glycemia were measured at various time points. The dynamics and morphology of macrophages in the diabetic thymus were investigated by histology, immunohistochemistry, qPCR, electron microscopy and flow cytometry. ResultsIn hyperglycemic animals the involuting thymus is gradually infiltrated by tissue macrophages (ED1-positive) and depleted of resident macrophages (ED2-positive). While ED1 positive macrophages are scattered in both cortex and medulla the ED2 positive ones are limited to the cortex and cortico-medullary junction. CD4+CD11b+macrophages also accumulate. The TUNEL reaction that detects the degradation of the DNA from apoptotic thymocytes in the macrophages is enhanced. The thymic macrophages enlarge and accumulate lipid vacuoles and apoptotic bodies. qPCR measurements of the expression of macrophage markers showed a persistent increase in the diabetic thymus after the injection of streptozotocin. ConclusionsThymus involutes rapidly and persistently after the onset of hyperglycemia because of the elevated apoptosis in the thymocytes. Tissue macrophages accumulate in the thymus and the resident macrophages decrease. This results in an overall increase in macrophage activity in the diabetic thymus in response to the elevated apoptosis of thymocytes produced by hyperglycemia.