...They are primarily associated with acute bacterial inflammation, and their reaction time is immediate, typically within one hour of tissue injury. Neutrophils are phagocytes, capable of ingesting microorganisms or particles. Each phagocytic event results in the formation of a phagosome into which reactive oxygen species and hydrolytic enzymes are secreted. Due to the consumption of oxygen during this event, a "respiratory bust" ensues. This "respiratory bust" in turn activates the enzyme NADPH oxidase, resulting in the production of large amounts of superoxide. The superoxide anion is subsequently converted to hypochlorous acid (HOCl) via the enzyme myeloperoxidate, which is presumed to result in the elimination of the phagocytized bacteria. (2)

The other two classes of granular leukocytes are the eosinophils and basophils. Eosinophils are activated during allergic diseases, infections, or other medical conditions, and elevated levels are associated with an allergic response or parasitic infestation. They contain coarse, cytoplasmic granules of uniform size and make up 1-3% of the total circulating leukocytes. Basophils have a nuclei size similar to eosinophils, however, when activated, they degranulate and release cellular components, including histamine and proteoglycans, stored within the granules, along with proteolytic enzymes. (2) They represent approximately 0.01-0.3% of the circulating leukocytes.

Interestingly, neutrophil activity has also been correlated with coronary artery disease. Sarndahl, et al., reported a significant reduction in neutrophillic ROS production in patients with stable coronary artery disease, noting a 30% [+ or -]17 mean reduction, compared to matched controls. It was also noted that as a consequence of non-receptor mediated response, a significantly lower neutrophillic ROS production ensued (a reduction of 21% [+ or -]12). (3) A separate study also noted a reduced capacity in the ability to up-regulate CD11b cells as well as to produce [H.sub.2][O.sub.2], both functional aspects of neutrophil activation, compared to healthy controls. (4)

All leukocytes have a minimal life span, and thus a high turnover rate. As such, they are extremely vulnerable to mineral, vitamin, and antioxidant deficiencies. The complex interplay between multiple cell types and intercellular messengers makes nutritional status both subtle and far-reaching, particularly when it involves immune activation.

Minerals Associated with Neutrophil Activation Chronic low-grade type infections, associated with neutrophil influx, are characteristic of a number of disease processes, ranging from periodontal infections and asthma to cardiovascular disease, pulmonary complications, and rheumatoid arthritis. Certain minerals play important roles in supporting optimal immune function. Zinc, copper, calcium, and phosphorous are particularly important mineral participants in this role.

Zinc: As an essential cofactor for over 70 enzymes, zinc is a vital component in immunocompetence. It is particularly important for highly proliferating cells including those of the immune system. Overt signs of zinc deficiency are numerous and have been well documented. They include atrophy of the thymus, spleen, and lymph nodes; decreased or delayed hypersensitivity response and allograft rejection; lowered production of B- and T-lymphocytes; decreased natural killer cell activity; decreased phagocytosis; and dcreased thymic hormone activity. (5, 6) A deficiency in zinc results in a rapid and extensive effect on the immune system (7) including decreased function of monocytes and macrophages, decreased phagocytosis of the neutrophil granulocytes, and decreased cytotoxicity of natural killer cells. (8) Additionally, the number and activity of NK cells have shown to be dependent upon the level of serum zinc. (9) Zinc malabsorption is evidenced by poor wound healing as well as an increased susceptibility to infections. Short periods of zinc supplementation have shown to substantially improve immune defenses, particularly in children, the elderly, and individuals with certain diseases including chronic gastrointestinal disorders. (10)

Copper: Anemia and neutropenia are two known hematological manifestations of copper deficiency. The phagocytic capacity of the neutrophil is markedly modified in copper insufficiency. (11) Neurological manifestations of copper deficiency have also been observed, a typical presentation being myelopathy. (12) Deficiencies in copper, in conjunction with other vitamin and mineral deficiencies, have been correlated with a loss of thymic cellularity, which results in a diminished differentiation of T-lymphocytes. Subsequently, a maturational defect in T-lymphocytes ensues, observed by a decrease in both total T-cells (T3 and rosette-forming T-cells), and in T4 helper/inducer cells. In mice deficient in copper, iron, and zinc, cytotoxic T-lymphocyte (CTL) activity...

NOTE: All illustrations and photos have been removed from this article.



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