Hyperglycemia and Some Aspects of Leukocyte Activation In Vitro

Area of Science:

• Immunology
• Endocrinology
• Biochemistry

Background:

• Diabetes mellitus is a metabolic disorder associated with immune dysfunction.
• Leukocyte functional status is altered in diabetes, impacting disease progression and complications.
• Understanding these alterations is crucial for developing targeted therapies.

Purpose of the Study:

• To analyze the functional status of blood leukocytes in patients with diabetes mellitus.
• To investigate the in vitro effect of glucose on leukocyte function.
• To assess the role of glucose in the activation of neutrophils and the formation of neutrophil extracellular traps.

Main Methods:

• Assessed reactive oxygen species (ROS) and reactive halogen species generation by monocytes and neutrophils using chemiluminescence assays.
• Stimulated leukocytes with phorbol 12-myristate 13-acetate (PMA) or opsonized zymosan.
• Evaluated neutrophil extracellular trap (NET) formation in blood samples after glucose addition.
• Compared leukocyte function between patients with diabetes mellitus and healthy donors.

Main Results:

• Leukocytes from patients with diabetes mellitus exhibited primed functional status compared to healthy donors.
• In vitro addition of glucose to blood from healthy donors mimicked the primed leukocyte status observed in diabetic patients.
• Glucose addition in vitro also triggered the formation of neutrophil extracellular traps in healthy donor blood.

Conclusions:

• Diabetes mellitus primes blood leukocytes, characterized by enhanced ROS and reactive halogen species production.
• Glucose plays a significant role in the observed leukocyte priming and neutrophil extracellular trap formation in diabetes.
• These findings suggest that hyperglycemia contributes to immune dysregulation in diabetes mellitus.