**4. Ascorbic acid and leukocyte function**

Leukocytes, like neutrophils and monocytes, contain higher ascorbic acid levels (about a hundred fold) than in plasma concentrations. Leukocytes contain maximal ascorbic acid's levels at intakes of about 0.1 g/day, although other cells likely need more ascorbic acid levels for saturation. Neutrophils accumulate ascorbic acid through Sodium-dependent Vitamin C Transporter (SVCT) and typically have intracellular concentrations minimal about 1 mM [14]. After releasing ROS, neutrophils elevate cellular level of ascorbic acid via non-specific uptake of the oxidized form, Dehydroascorbate (DHA), through Glucose Transporters (GLUT). DHA is then quickly decreased to ascorbic acid intracellularly, to provide concentrations of about 10 mM, and ascorbic acid exhibits pivotal effects in the related cells. Neutrophils that have sufficient levels of ascorbic acid are postulated to defend from ROS destruction [14]. As a vigorous water-soluble antioxidant, ascorbic acid may also scavenge numerous ROS and rejuvenate the pivotal function of some antioxidants, such as glutathione and vitamin E. Ascorbic acid is depleted from neutrophils in an oxidant-dependent pathway after phagocytosis or activation with soluble inductions [14–16].

The transcription factor Nuclear Factor кB (NFкB) was a pivotal part in the pro-inflammatory response due to the homeostasis imbalance between oxidant production and antioxidant protections. Oxidants can initiate NFкB, that activates a signaling pathway, directing to generation of ROS and other inflammatory mediators [14]. Ascorbic acid has been exhibited to influence both oxidant production and NFкB induction in dendritic cells in vitro, as well as in PMN leukocytes. The cells, with Thiol-containing proteins, can be specifically susceptible to redox changes, and they are frequently crucial for controlling redox-related cell signaling pathways. T-cells have been used to study the ascorbic acid-dependent regulation of thiol-dependent cell signaling and gene expression pathways [14–16].

As a conclusion, the regulation of immune function by ascorbic acid through stimulation of redox-sensitive cell signaling cascades or directly defending pivotal cell parts [14]. The exposure of leukocytes (neutrophils and monocytes) to oxidants may suppress cell motility, which is believed to be caused by lipid peroxidation and their effects on the fluidity of cell membranes. Because neutrophils have elevated concentrations of polyunsaturated fatty acids in their plasma membranes, an increase in neutrophil motility observed after ascorbic acid intake may be associated with oxidant scavenging, such as vitamin E rejuvenation [14, 16].
