Mast Cell Precursors and Diabetic Neuropathy—Is Immunity the Connection?

Abstract

Introduction: Diabetic neuropathy and distal foot lesions are common complications of type two diabetic patients (T2DM), however the underlying pathophysiology remains uncertain. Mast cells (MCs) provide a possible link with immunity and neuroinflammation. These cells of innate immune system are found near sensory nerves or the endoneurial compartment, where they differentiate and participate in innate host defense reactions. MCs are involved in wound healing, but their role in diabetes is unknown. Aim: To evaluate a possible connection between peripheral bone marrow derived blood MC precursors and diabetic neuropathy without and with ischemic skin lesions. Methods: We enrolled 26 healthy controls (C), 15 T2DM with peripheral sensimotor neuropathy (N) and 14 T2DM with neuropathy, distal ischemia (allux oximetry <30 mm Hg) and foot lesions (N1). Peripheral blood was analysed by flow-cytometry (CD34, CD117, lineage cocktail 1 and FcεRI antibodies). Results: We found a significant decrease of MC precursors (LIN-, CD34+, CD117+, FcεRI+ cells) in N and N1 (0.00and 0.00051% of mononuclear cells vs. 0.0018% in C, p<0.04). MC number directly correlated with total lymphocyte (p<0.005, R =0.474) T-lymphocyte (p<0.005, R =0.396) and CD4+ T-lymphocyte (p<0.0005, R =0.515) numbers. There was an inverse but not significant correlation with monocytes (p=0.073, R =0.197). Conclusions: Our results show a possible involvement of MC precursors in human neuropathy and neuroischemic diabetic foot lesions. Conceivably, MCs could have a protective role in favoring wound healing by interaction with cells such as fibroblasts, endothelial, immune, nervous and epithelial cells and by release mediators and neurotransmitters. The correlation with T-lymphocytes might explain the impaired wound healing in N1, suggesting a direct contact between the two populations at the lesion site. Although not significant, the inverse relation with monocytes could be i up-regulated by the decrease in MC precursors. Disclosure M. Sambataro: None. L. Sambado: None. E. Trevisiol: None. A. Paccagnella: None.