Ascorbate sustains neutrophil NOS expression, catalysis, and oxidative burst

Area of Science:

• Immunology
• Nutritional Biochemistry

Background:

• In vitro studies show ascorbate enhances neutrophil nitric oxide (NO) and oxidative burst.
• The in vivo role of ascorbate in neutrophil function requires further investigation.

Purpose of the Study:

• To assess the impact of in vivo ascorbate deficiency on guinea pig neutrophils.
• To evaluate neutrophil ascorbate and tetrahydrobiopterin levels, NOS expression/activity, phagocytosis, and respiratory burst.

Main Methods:

• Guinea pigs were subjected to ascorbate deficiency (scurvy).
• Neutrophil functions including NO generation, free radical production, and phagocytosis were measured.
• In vitro supplementation with ascorbate and tetrahydrobiopterin was performed.

Main Results:

• Ascorbate deficiency reduced neutrophil ascorbate, tetrahydrobiopterin, NOS expression/activity, and NO/free radical generation.
• In vitro supplementation partially restored NOS catalysis and NO generation but not to control levels.
• Phagocytosis was unaffected, but free radical generation was compromised in scorbutic neutrophils.
• Ascorbate-induced free radical generation is NO-dependent and relies on ascorbate recycling.

Conclusions:

• Ascorbate deficiency impairs neutrophil oxidative microbicidal actions in vivo.
• Ascorbate plays a novel role in augmenting both NOS expression and activity.
• Ascorbate recycling is crucial for neutrophil oxidative burst augmentation.