FMLP-, thapsigargin-, and H2O2-evoked changes in intracellular free calcium concentration in lymphocytes and neutrophils of type 2 diabetic patients

Shanti S. Kappala, Javier Espino, Jose A. Pariente, Ana B. Rodriguez, Satyan Rajbhandari, Arati Iyengar, Keshore R. Bidasee, Jaipaul Singh

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Type 2 diabetic (T2DM) patients are immune-compromised having a higher susceptibility to infections and long-term complications in different parts of the body contributing to increased morbidity and mortality. A derangement in the homeostasis of intracellular free calcium concentration [Ca2+] i is known to be associated with several diseases in the body including T2DM. Both neutrophils and lymphocytes play active protective roles in host immune response to infection showing impairment in microbicidal functions including phagocytosis and chemotaxis which are calcium-dependent processes. This study evaluated the process of [Ca2+]i mobilization from both neutrophils and lymphocytes taken from blood of both T2DM patients and healthy age-matched control subjects investigating the effect of N-formyl-methionyl-leucyl-phenylalanine (fMLP), thapsigargin (TG), and hydrogen peroxide (H2O2) on [Ca2+]i homeostasis. This study employed isolated peripheral blood neutrophils and lymphocytes from 24 T2DM patients and 24 healthy volunteers. Either neutrophils or lymphocytes were stimulated separately with fMLP, TG, or H2O 2. Induced changes in [Ca2+] in both neutrophils and lymphocytes were evaluated using spectrofluorometric methods. Stimulation of human neutrophils and lymphocytes with fMLP, TG, or H2O2 in the presence of [Ca2+]o resulted in significant decreases in [Ca2+]i mobilization from T2DM patients compared with healthy controls. These data indicate that neutrophils and lymphocytes from T2DM patients are less responsive to calcium mobilizing agents compared with granulocytes from healthy controls and this is possibly due to the hyperglycemia. The results suggest that agonist-evoked decrease in [Ca 2+]i in immune cells might be one of the possible mechanisms of impaired immunity in diabetic patients.

Original languageEnglish (US)
Pages (from-to)251-260
Number of pages10
JournalMolecular and cellular biochemistry
Volume387
Issue number1-2
DOIs
StatePublished - Feb 2014

Keywords

  • Agonists
  • Cytosolic calcium
  • Lymphocytes
  • Neutrophils
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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