Dysregulation of intracellular Ca2+ in lymphocytes and neutrophils in type 2 diabetic patients (1072.11)

Abstract

Background: Patients with T2D are immune‐compromised, making them more susceptible to infections and long term complications than non‐diabetic individuals. Neutrophils and lymphocytes play key roles in host‐immune responses to infections, and their phagocytic and chemotatic activities are reduced in diabetes. To date, the underlying causes for impairment in neutrophils and lymphocytes functions in T2D remain poorly defined. Dysregulation of intracellular Ca2+ cycling is a common phenotype in many diabetic cells. This study investigated if intracellular Ca2+ cycling is also defective in neutrophils and lymphocytes isolated from individuals with T2D.Methods and results: Neutrophils and lymphocytes were obtained from patients with T2D and healthy controls with consent, and their intracellular Ca2+ cycling kinetics when challenged with thapsigargin (TG), formyl‐methionyl‐leucyl‐phenylalanine (fMLP) and hydrogen peroxide (H2O2), were compared using time‐lapsed Ca2+ imaging assays. All cells from T2D and control patients responded to TG, fMLP and H2O2. However, the rate of cytoplasmic Ca2+ rise, peak Ca2+ transient amplitude and Ca2+ transient decay times were significantly compromised in neutrophils and lymphocytes from T2D patients compared to healthy controls.Conclusion: From these data we concluded that neutrophils and lymphocytes from T2DM patients are less responsive to this wide array of intracellular Ca2+ mobilizing agonists compared to control. Moreover, the decreased [Ca2+]i in immune cells might be one of the possible mechanisms of impaired immunity in diabetic patients.