**4.1 Neutrophil chemotaxis**

A beginning part in non-specific immunity is started by neutrophil infiltration into infected tissues as the effect from pathogen- or host-derived inflammatory signals such as *N*-formylmethionyl-leucyl-phenylalanine (fMLP), IL-8, leukotriene B4, and complement component (C5a). The chemotaxis' migration of neutrophils in response

to chemical stimuli, may be randomly, is as named chemokinesis [14, 17]. Neutrophils expressed over than 20 different chemokine and chemoattractant receptors to recognize and quickly reciprocate to tissue destruction signals. The scorbutic guinea pigs' study showed a damaged leukocyte chemotactic response compared with leukocytes isolated from animal models administered with ascorbic acid in the intake. These suggest that ascorbic acid depletion may affected on the function of phagocytes to migrate to inflammatory areas [14, 15, 18].

Neutrophils may get "paralysis," especially in patients with severe inflammatory condition and associated with compromised neutrophil chemotactic's dysfunction [14]. These neutrophils are the part of the increased levels of immune-suppressive and anti-inflammatory mediators (such as IL-4 and IL-10) during the compensatory antiinflammatory response seen after primary induction of the immune system. It is also a possibility, that ascorbic acid deficiency may associated and is common during severe infection. The previous researches showed that recurrent infections had damaged leukocyte chemotaxis, which could be regenerated in return to administration with gram doses of ascorbic acid. Furthermore, neonates with systemic infections injected with 0.4 g/day of ascorbic acid, dramatically increased neutrophil chemotaxis [14, 18].

The genetic disorders of neutrophils' function may also contribute to recurrent infection. The cases of Chronic Granulomatous Disease (CGD), an immunodeficiency disorder, resulting in the reducing of leukocyte production of ROS, and Chediak-Higashi Syndrome (CHS) as a rare autosomal recessive disease, is associated with vesicular transport trafficking and decreased neutrophils' mobility [14]. Ascorbic acid may promote the action of unnecessary antimicrobial mechanisms in these cells, although ascorbic acid supplementation would not be expected to influence the elemental disorders of these genetic diseases. Patients with CGD showed increased leukocyte chemotaxis following ascorbic acid intake were related with reduced infections and clinical improvement. The improvement of neutrophils's chemotaxis was reported in a mouse model of CHS following ascorbic acid administration. Besides, neutrophils isolated from two children with CHS exhibited enhanced chemotaxis after administration with 0.2–0.5 g/day ascorbic acid. The ascorbic acid-dependent improvement of chemotaxis was assumed to be treated in part through the results on microtubule assembly, and has showed that intracellular ascorbic acid may repair microtubules [14, 15, 18].

The healthy persons that take ascorbic acid have also been recorded to boost neutrophils chemotactic function, that associated with the antihistamine effect of ascorbic acid [14]. A dietary source of ascorbic acid (providing 0.25 g/day) supplementation, to inadequate ascorbic acid status (i.e., <50 μM) persons, resulted in a 20% elevate in neutrophils chemotaxis. A combine administration of elderly women with 1000 mg/day of ascorbic acid and vitamin E increased neutrophils functions. Thus, ascorbic acid administration provides benefits in boosting the immune system, especially for an inadequate ascorbic acid status, and can be more frequent in the aged. Although, it should be notable that it is not yet convinced to what extent increased ex vivo leukocyte chemotaxis results into enhanced in vivo immune activity [14, 18].
