Effect of acetylsalycilic acid (aspirin; Ron-Pulenk) on activity of mouse neutrophil peroxydase system was investigated. Using luminol-dependent chemiluminscence and cytochemical methods we demonstrated that neutrophil peroxydase system in mice receiving aspirin for 14 days is probably determined by stimulation of myeloperoxydase synthesis.

The effects of hypolipidemic drug clofibrate and polypeptide dalargin on activity of the neutrophil peroxidase system in mice were studied using the method of luminol-enhanced chemiluminescence. Clofibrate and dalargin increased the chemiluminescence of mouse whole blood. Their combined use several-fold potentiated this effect. It is expected that combined use of hypolipidemics and polypeptides will open a new trend in the search for stimulators of oxygen-dependent nonspecific immunity.

The effect of SO 3 2− , S2−, NO 3 − , and NH 4 + on activity of the peroxidase-hydrogen peroxide system in human peripheral blood neutrophils was studied by the cytochemical method. We showed that the effect of these xenobiotics on neutrophils is similar to that on plants.

Activity of the peroxidase-hydrogen peroxide system is proposed as a biological marker of ecological risk of heavy metal contamination of the environment. The effect of lead, copper, mercury, and cadmium ions on peroxidase system activity in human peripheral blood neutrophils was studied using cytochemical methods. A possible mechanism of suppression of peroxidase system activity by metal ions is discussed.

The transformation of nascent phagosomes into forms capable of interacting with antimicrobial organelles of phagocytes, peroxisomes, depends on certain interactions between phagosomes and other vacuolar organelles. Phagosomes repeatedly interact with early and late endosomes through temporary contacts, which allows them to gain and lose complex sets of proteins. In addition, certain polypeptides are eliminated from phagosomes through recycling. New proteins enter phagosomes from the organelles of the biosynthetic pathway or are recruited from the cytoplasm. In addition, phagosomes receive proteins in the process of interaction with endosomes. The overall result of such transformation is acquiring new properties that make possible their interaction with peroxisomes.

Myeloperoxidase is the main peroxisomal protein of neutrophils, monocytes, and a subpopulation of tissue macrophages; it plays the key role in protective and inflammatory responses of the organism. This role is mediated by various diffusible radicals formed during oxidative reactions catalyzed by the enzyme heme. Myeloperoxidase and nitric oxide synthase are stored in peroxisomes. Nitric oxide reacts with the heme of myeloperoxidase. Low nitric oxide concentrations increase peroxidase activity through reduction of Compound II to native myeloperoxidase. Conversely, high nitric oxide concentrations inhibit the catalytic activity of myeloperoxidase through formation of inactive nitrosyl–heme complexes. Such effect of nitric oxide on catalytic activity of myeloperoxidase has various consequences for infectious and local inflammatory processes. Another oxide of nitrogen, nitrite, is a good substrate for myeloperoxidase Compound I but slowly reacts with Compound II. Nitrogen dioxide is formed after nitrite oxidation by myeloperoxidase. Formation of nitrogen dioxide is another protective mechanism and nitration of microbial proteins by myeloperoxidase can represent an additional protective response of peroxisomes.

The neutrophil contains numerous granules of various composition and structure. For decades, the neutrophil was believed to contain only two granule types, peroxisomes, or peroxidase-positive granules, and peroxidase-negative granules. Later, existence of the third type distinguished by the presence of gelatinase hydrolyzing collagen and gelatin was proposed. Gelatinase was found in the granules that are lighter as compared to the common peroxidase-negative granules and represent their subpopulation. In addition to gelatinase, these granules contain beta-2 microglobulin, cytochrome b558, as well as receptor and adhesion proteins. Upon stimulation by inflammatory mediators, the gelatinase granules are secreted before the common peroxidase-negative granules. Their exocytosis mediates delivery of new adhesion proteins to the plasma membrane, which is required for maintenance of permanent and fast cell adhesion to the endothelium. The released gelatinase allows the neutrophil to penetrate through the basement membrane of the endothelium.

Peroxisomal myeloperoxidase plays a key role in synthesis of oxidants by neutrophilic leukocytes. This heme protein consists of two subunits connected by a disulfide bond. The enzyme uses Н2О2 and Сl– for synthesizing HOCl, the major oxidant produced by neutrophils. In addition to the chlorination reaction, myeloperoxidase exhibits some other properties depending on its oxidation state. The enzyme significantly affects synthesis of oxidants in the cells depending on the competing substrate concentrations and other factors. О⋅¯2 is also a physiological substrate of myeloperoxidase. Its reaction with the enzyme determines how the cells utilize О⋅¯2 for pathogen elimination. О⋅¯2 affects the chlorinating and peroxidase activities of myeloperoxidase. In addition, О⋅¯2 reacts with the enzyme yielding the catalytically active compound III that hydroxylates phenols.

Myeloperoxidase plays the key role in antimicrobial of phagocytes. This enzyme uses hydrogen peroxide and chloride to catalyze hypochlorous acid formation. HOCl is the most probable agent in the oxygen-dependent bactericidal activity in the phagocyte phagosome. Chlorination markers indicate HOCl generation in the quantities lethal for bacteria. Enzymatic assay for myeloperoxidase indicates proceeding of other reactions involved in bactericidal activity. Superoxide integrates many activities of this kind and is important for physiological function of myeloperoxidase. Elucidation of phagosomes biochemistry can help us to understand why certain pathogens survive in such unfavorable environment.

Myeloperoxidase plays the key role in antimicrobial oxygen-dependent activity of neutrophils. This heme-containing enzyme catalyzes HOCl formation from H2O2 and Cl–. HOCl is a strong oxidation agent produced at the significant level by neutrophils. Myeloperoxidase easily oxidizes thiocyanate to hypothiocyanate and Br– to HOBr, which are involved in protective reactions. Myeloperoxidase reacts quickly with nitric oxide and peroxynitrite in inflammation foci. All these reactions affect neutrophil-induced oxidative stress.

The effect of rare metal ions on the activity of the peroxidase system in Pisum sativum L. roots was studied by luminol-dependent chemiluminescence. Trivalent ions of scandium, gallium, indium, and lanthanum, to different extents, inhibit the chemiluminescence of damaged P. sativum roots. A decreased generation of superoxide due to the formation of the complex between metal ions and NADP can underlie the inhibited activity of peroxidase system. The possible mechanism of inhibition of the peroxidase system activity by metal ions is discussed.

Peroxisomes of neutrophils are formed in promyelocytes. In addition to myeloperoxidase constituting 35% peroxisomes, they contain nonenzymatic antimicrobial cationic peptides and polypeptides, several serine proteases, as well as some other hydrolases and additional components. Similar to serine proteases, these hydrolases can serve as natural antibiotics. Their function can complement the main oxidation function of neutrophilic myeloperoxidase in the protective response. The peroxisomes contain acid glycosaminoglycans functioning as an anionic carrier that reversibly binds cationic proteins, including hydrolases.

Our knowledge on the nature and quantity of reactive O2forms generated in phagocytes, particularly in neutrophil leucocytes, and their role in nonspecific immunity is reviewed. In thermodynamical terms, oxygen is a very reactive molecule and, hence, can react with most chemical elements and many organic molecules. In kinetic terms, O2is rather inert. Its reactivity can be increased either by reduction or excitation. After accepting four electrons, O2is finally reduced to H2O. Partial reduction resulting in highly reactive intermediates, namely, superoxide anion (O2·–), hydrogen peroxide (H2O2), and hydroxyl radical (·OH), is possible. Singlet oxygen (1O2) is the product of O2excitation. Phagocytes acting like agents of nonspecific immunity generate such reactive forms of O2.

Rb+ at concentrations 10(-3) 10(-4), and 10(-5) M increased luminol-dependent chemiluminescence in pea roots, while Li+ at 10(-1), 10(-2), 10(-3), and 10(-4) M decreased it. These data, correlated to the influence of Li+ and Rb+ on luminol-dependent chemiluminescence of the neutrophils during phagocytosis, support the concept of the universal nature of the peroxidase system in plant and animal cells.

A critical survey of data confirming the concept of the existence of peroxidase-containing secretory bodies, peroxidasosomes, in plant cells is presented. Problems of the subcellular distribution of peroxidases in the cells of higher and lower plants are highlighted. Cofactors of cell peroxidase systems in lower plants and the problems of hydrogen peroxide generation are discussed. Functional properties of peroxidase-containing organelles have been described in the case of infection or trauma. The presence of non-enzymatic cationic proteins with bactericidal functions similar to the proteins present in leucocyte peroxidasosomes is discussed.

The effects of fabric dyes (16 items), heavy metal ions (Cd2+, Pb2+, Sn2+, Hg2+, and Cu2+) and gaseous waste of steam power plants (H2S, SO2, NO, NH3) on the peroxidase-dependent immunity in Pisum sativum were studied using the method of luminol-enhanced chemiluminescence. Copper compares to mercury according to its toxicity. The fabric dyes at 10(-5) M decrease the chemiluminescence of plants by 50%. Hydrogen sulfide is the most toxic among gaseous wastes. Since the peroxidase system plays an important role in the struggle of plants against various infections, it is necessary to monitor the effects of xenobiotics dissolved in water on plant immunity.

We present more accurate evidence for generation of endogenous hydrogen peroxide as a result of peroxidase - endogenous hydrogen peroxide system activity in the neutrophils (Rogovin et al., 1978). The normal cytochemical reaction of the peroxidase - endogenous hydrogen peroxide system in the neutrophil peroxidasosomes after elimination of weter-dissolved H2O2 by KMnO4 indicates the neutrophils on smears as a source of H2O2, rather than alcohol-formaldehyde. This is confirmed by the cytochemical reaction of peroxidase - endogenous H2O2 reaction in the neutrophils on smears prepared without fixation. The peroxidase - endogenous H2O2 system in the neutrophils on blood smears acts at pH other than peroxidase: 7,7-5,5 vs. 7,7-3,4 (basic pH range was not examined). This difference appear to be due specific features of the enzyme complexes ultimately generating H2O2.

The opinion is presented that, in several types of cells, a hyperautophagic activity of lysosomes underlies, the Chediak - Higashi syndrome in humans and its analogues in animals.