PEROKSIDAZOSOMY — a special TYPE of the secretory organellas containing peroxidase and systems of generation of hydrogen peroxide. Possess pronounced antimicrobic function.
Are opened in 1972 by V. Rogovi-ny with sotr. Long time of peroxide-zosoderzhashchiye of a granule of leukocytes were considered as typical primary lysosomes (see). By means of a double electronic cytochemical change on acid phosphatase and peroxidase not lysosomic nature of these granules was established what preferential separate distribution of enzymes on cellular organellas testified to: acid phosphatase was in elements of a complex of Golgi (see Golgi a complex), and peroxidase — in azurophilic granules of neutrophils (tsvetn. the tab., Art. 400, fig. 23 and 24) willows specific granules of eosinophils (see Leukocytes). Absence in the nature of organellas, unique for this cell, that allowed to combine peroxide zosoderzhashchy granules of neutrophils and eosinophils with all other peroksidazoso-holding granules] secretory cells in one group of organellas — peroksidazosoma was postulated.
The original positions of peroxide-zosomnoy of the concept which are put forward by domestic researchers in 1972 are confirmed with various schools of foreign researchers. In 1979 at fractionation of homogenates of leukocytes Rastin and Peters (G. J. Rustin, T. J. Peters) confirmed separate distribution of acid phosphatase and peroxidase. Similar distribution of these enzymes on fractions is established by Dzhellink (R. to H. Jellinck) with sotr. (1976) also in epithelial cells of a mucous membrane of a uterus. Dyumon (A. Dumont, 1978) and De Hir (E. De of Neeg, 1980) with sotr. during the studying of macrophages came to a conclusion about lack of communication between bactericidal activity of these cells and lysosomes. Group of English researchers led by Segal (A. W. Segal, 1980) during the studying of neutrophils of the person came to conclusion that lysosomes represent special group of the granules containing not peroxidase, but acid hydrolases to-rye as earlier assumed, contain together with myeloperoxidase in azurophilic granules. Thus, these researchers also came to denial of the lysosomic nature of peroksidazosoderzha-shchy azurophilic granules of neutrophils. L. A. Piruzyan and V. A. Fomina (1980), and also Shannon and Tsellmer (W. A. Shannon,
D. The m of Zellmer, 1981) by means of electronic and cytochemical researches in neutrophils and monocytes were found typical lysosomes (see. Cytochemical methods of a research). Thus need of unreasonable transfer of properties of these of peroxide-zopolozhitelnykh of granules on real lysosomes finally disappeared.
Items essentially differ not only from lysosomes, but also from the peroxisomas (see the Cell) which are characterized by the maintenance of special oxidases (see) and catalases (see). Peroxisomas unlike P. are formed of tanks only smooth endoplasmas to an aticha with by about a reticulum (see), and their proteins do not pass through Golgi's complex. Peroxisomas are surrounded with an elementary membrane, their average diameter is equal
of 529 0,5 microns. They quite often contain a dense paracrystal core. Peroxisomas are eurysynusic in the nature: they are found in animal, plant cells and unicells. Function of peroxisomas still is up to the end not found out. However it is known that peroxisomas participate in metabolism of lipids (see). They contain active system of beta oxidation of fatty acids. Peroksisomny enzyme of di-gidroksiatsetonfosfatatsetil a trance - a feraza participates in biosynthesis of ethers glitsero a lipid. It is shown that peroxisomas play also important role in a gluconeogenesis (see Glycolysis), participate in metabolism of purines, oxidation of ethanol and methanol. Energy of peroksisomny oxidation does not collect in the form of ATP and is distinguished in the form of heat.
It is necessary to pay attention to historically developed similarity of the terms «peroxisomas» and «peroksi-dazosoma». However the term «peroksi-dazosom» reflects the name of the main enzyme concluded in an organella and causing its specifics.
The following components enter into P.'s structure of neutrophils and other types of cells: peroxidase, enzimaticha
of Skye system of generation of hydrogen peroxide, haloid cofactors (iodide, chloride, bromide) or thiocyanate, not euzymatic cationic proteins, mucopolysaccharides, minor amount of not lysosomic acid hydrolases.
Process of education of P. goes according to the classical scheme of Peleyd for secretory granules: synthesis of components P. in channels of an endoplasmic reticulum, packaging in elements of a complex of Golgi, an otpochkovyvaniye from them unripe P. with the subsequent maturing (consolidation), their accumulation and secretion after receipt of the corresponding incentive. Secretion of contents of P. of neutrophils, eosinophils, mononuclear phagocytes happens at contact with the corresponding particles, opsonizirovanny immunoglobulins, acinous cells of the lacrimal and sialadens — at nervous stimulation, and on elekt-rofiziol. reminds parameters secretion of chromaffin granules of cells of an adrenal gland and synoptic bubbles of neurons (see Secretion). It is necessary to emphasize that unlike P. contents of lysosomes are not allocated from intact cells. Items have the general components with other types of secretory granules (containing, e.g., mucopolysaccharides and nelizosom*yay acid hydrolases), but unlike them are characterized by existence of pronounced protective antimicrobic function.
Items are eurysynusic in the nature. At the person and animals of G1. are available in neutrophils, eosinophils, basophiles, mast cells, mononuclear phagocytes, acinous cells of salivary, lacrimal and mammary glands, epithelial cells of a mucous membrane went. - kish. a path, respiratory tracts, a uterus, epithelial cells of gyrose tubules of kidneys, follicular cells of a thyroid gland, etc. Peroksidazo-somy exist in all cells where there is a peroxidase (see Peroxidases) as presence of this enzyme demands existence of euzymatic system of generation of hydrogen peroxide since peroxidase in zooblasts does not function without regulated (i.e. enzymatic) supply of hydrogen peroxide. The Peroksidazny systems P. including peroxidase, system of synthesis of hydrogen peroxide, the oxidized cofactor (iodide, chloride, bromide or thiocyanate) function as follows: peroxidase
activates hydrogen peroxide, reacts edges with haloids or thiocyanate; the metabolite which is formed at the same time (intermediat) has properties, toxic for microorganisms. Other component P. — cationic not euzymatic proteins — connects to anion components on a surface of microorganisms and breaks their normal life activity. Such cationic proteins are secreted in phagosomas that is proved with the help gistokhy. methods. It is established that cationic proteins P. of neutrophils and eosinophils are toxic as well for helminths. At combined action of peroksidazny systems and cationic not euzymatic proteins it is observed how showed And. G1. Ashmarin (see t. 10, additional materials),
S. N. Lyzlova and other researchers (1974), accurately expressed synergism in bactericidal action.
One more component P. are mucopolysaccharides (see), to-rye interfere with an attachment of bacteria to mucous membranes.
II. differ from lysosomes and the fact that mucopolysaccharides are not found in lysosomes.
Minor (extremely insignificant) amount of not lysosomic acid hydrolases (see), to-rye in view of neutral pH outside a cell support Nek-rye P., and also in phagosomas cannot function after secretion. Besides, oxidases-nye of system P. have an inhibiting effect on acid hydrolases. Thus, not lysosomic acid hydrolases P. should be considered a biochemical rudiment of acid hydrolases phylogenetic of more ancient lysosomes, from to-rykh as C. de Duv and Vatyo consider (R. Wattiaux, 1966), there were all secretory granules.
Components P. can function as it is intracellular (e.g., in leukocytes), and out of cells (follicles of a thyroid gland, an oral cavity, a gleam of a large intestine, milk). In Kupfer's cells, bryushnopolostny, alveolar macrophages and monocytes of G1. carry out antimicrobic, anti-fungal, anti-virus and, perhaps, antineoplastic function. Similar protective function is performed by P. of sialadens and an epithelium of a large intestine (i.e. at the beginning and at the end went. - kish. path), ferruterous epithelium of a uterus and mammary gland. At this P. of cells of a mammary gland can provide bacterial action of milk and protect tissue of a mammary gland from a microbic invasion at suction. Thus, peroksidazosoma are presented preferential in those cells, to-rye dangers of a microbic invasion are substantially subject or resist to it. If lysosomes can attribute preferential autofagovy role including processing and a reutilization of the material damaged or unnecessary a cell, then II. carry out first of all accurately expressed protective, antimicrobic, and also metabolic function and, perhaps, participate in mechanisms of digestion.
Understand protection of an organism against a bacterial, virus, mikoplazmati-chesky, fungal and protozoan invasion, and also against effect of toxins of bacteria as antimicrobic function; under metabolic function — participation in synthesis and catabolic transformations of hormones, various metabolites and other simple and complicated molecules; under digestive — the function aimed at providing an organism with plastic and power materials. However such division is a little conditional. So, one of undoubted antimicrobic functions of peroksidazny system — oxidizing decarboxylation and to a misinformation in and r about in and N iye and m in about to is lot of bacterial proteins — is at the same time and digestive function. Digestive activity of P. at the level of a complete organism (in went. - kish. a path) specially it was not studied, but impact of the IL components of granulocytes and acinous cells of sialadens on an iishcha in went. - kish. a path can be analogous to their influence on bacterial proteins. From the specified three functions of the Item one can prevail, others depending on type of a cell and from performance of specialized function by it in an organism can be transformed or oppressed (to be repressed). In nek-ry cells (granulocytes, macrophages) P. as secretory granules can interact with phagosomas. Items can also function, without being allocated from a cell and without merging with phagosomas, e.g., at metabolism of oestradiol in eosinophils and in epithelial cells of a mucous membrane of a uterus or in the course of synthesis of yodoprotein in neutrophils.
Three types of the animal peroxidases differing on the molecular weight (weight), catalytic properties and on specificity of action are studied:
myeloperoxidase (MLP), lactoperoxidase (LP) and ti-roidoperoksidaz (TP). Peroxidases are histochemical found in many fabrics and types of cells, but the peroxidases given about presence received biochemical and gistokhy. by methods, demand critical evaluation since psevdoperoksidazny activity gems and metals, hemoglobin, a myoglobin, tsitokhroma, cytochrome oxydase, a catalase and peroxides of lipids have. Therefore the most reliable data about intracellular localization of endogenous peroxidase can be obtained only at coincidence biochemical, gistokhy. and electronic tsi-tokhimicheskikh data.
In a number of types of cells (neutrophils, eosinophils, mononukleara, epithelial cells of a mucous membrane of a uterus, etc.) also the second component of peroksidazny system P. — system of generation of hydrogen peroxide is described. The first Beynton and Farkuer noted presence of hydrogen peroxide at pe-roksidazopolozhitelny granules of neutrophils (D. F. Bainton, M. of G. Farquhar, 1968). Afterwards such data were obtained on P. of other types of cells (neutrophils of the person, eosinophils, acinous follicular cells of salivary and lacrimal glands, cells of a thyroid gland, etc.).
Phagocytal activity of neutrophils and other phagocytes is followed by sharp increase in oxygen consumption and activation of oxidizing metabolism, insensitive to an inhibiting effect of cyanides. The consumed oxygen depending on type of a cell by means of special enzymes to a greater or lesser extent is transferred to hydrogen peroxide. In nek-ry types of cells one of such enzymes is NADFN-oksidaza. Correlation between the strengthened generation of hydrogen peroxide and activity NADFN-oksidazy is established. At the SI singing of activity NADF-oksi-dazy — the key process leading to the increased oxygen consumption, strengthening of formation of hydrogen peroxide and NADF+. Under these conditions the recovered NADF (NADFN) is formed in the course of oxidation of glucose (see) via the gek-sozomonofosfatny shunt; for two key enzymes of the shunt (a gluco-zo-6-phosphate-dehydrogenase and a 6-phospho-gluconate-dehydrogenase) NADF+ is a cofactor. Therefore functioning of the geksozomonofosfatny shunt in such cells is connected with activation NADFN-oksidazy. At phagocytosis activity of the geksozomonofosfatny shunt increases in leukocytes. Value of intensive metabolism of glucose via the geksozomo-nofosfatny shunt consists in the increased generation of hydrogen peroxide and NADF+, and the last, in turn, increases activity of the hexamonophosphatic shunt. Similar euzymatic systems of generation of hydrogen peroxide are found also in other types of cells.
The third component of peroksidazny systems — the oxidized cofactors which are directly connected with P.'s functioning — haloids (iodide, chloride, bromide) and thiocyanate. Many types of cells containing peroxidase selectively accumulate these cofactors. Neutrophils, e.g., selectively accumulate, especially in the activated state, thyroxine and triyodotironin. Iodide and thiocyanate collect in cells of salivary and mammary glands (in the concentration sufficient for effective functioning of pe-roksidazny systems), and chloride — in granulocytes and other types of cells.
Various types of cells contain peroksidazny systems with one or several of the specified cofactors. In neutrophils and mononuclear phagocytes systems myeloperoxidase — hydrogen peroxide — haloid (iodide, chloride) are known. Such systems, as a cofactor in to-rykh serves iodide or chloride, have antimicrobic effect at the expense of the yodi-nation of bacterial proteins, oxidations of sulphhydryl groups, oxidizing deamination and decarboxylation of amino acids of bacterial proteins.
The Peroksidazny system with chloride, besides, has antimicrobic effect and due to education of such bactericidal agents as aldehydes and chloroamines of amino acids, as well as due to education in system of a number of bactericidal metabolites of oxygen — anion-ra-
ticked superoxide (b2 ~), singlet oxygen, or the superoxidic radical (02) and the hydroxylic radical (IT).
The same systems participate also in exchange processes. So. the system myeloperoxidase — hydrogen peroxide — iodide participates in synthesis of yodotironin (in particular, a triyodo-tironina), binding of oestradiol, deamination of a histamine, inactivation of chemotactic factors, antitrypsin, etc. Metabolic and antimicrobic activities of peroxide of zny systems are closely connected with each other, and they can be divided conditionally taking into account the moment fiziol. activities of this cell and fiziol. activities of an organism in a certain time term. So, at pregnancy peroksidazny systems inactivate excess amount of female sex hormones and at the same time oestradiol increases antimicrobic activity of peroksidazny system of neutrophils in this critical period.
Except miyeloperoksidazny systems P., also others are known: the laktoperoksi-dazny systems functioning in acinous cells of salivary, lacrimal, mammary glands, in an epithelium of a mucous membrane of a uterus, intestines, and also in eosinophils and playing an antimicrobic and metabolic role, and tiroidoperoksidazny system, edges plays only a metabolic role. Antimicrobic activity of laktoperoksidazny systems is caused by a galogenization of bacterial proteins and toxins, inclusion in them of thiocyanate, oxidation of sulphhydryl groups, an inactivation of a bacterial hexokinase, pe-reoxidation of lipids with education ma a londia of a ldegid, hypothiocyanate and a tiotsianogen. The same systems perform a number of metabolic functions: participate in synthesis of yodotironin, oxidize estrogen, participate in synthesis of dityrosines in collagen of a uterus, than its rigidity during pregnancy, etc. speaks. And in this case it is difficult for an otdato pour antimicrobic activity from metabolic. On the contrary, for tiroido-peroksidazny systems of cells of a thyroid gland only its metabolic function — participation in synthesis of hormone is known. During the functioning of this system activated by thyritropic hormone there is an oxidation of iodide to reaktivno high valence state of iodine, the subsequent yodination of the tirozil-ny remains of a tiroglobulin, formation of thyroxine (T4) and triyodo-tironin (T3) by means of oxidizing interface of yodotironin. As well as in granulocytes, at activation of epithelial cells there is a stimulation of generation of hydrogen peroxide which also have enzymatic character. According to one researchers, generation of hydrogen peroxide depends from NADFN-oksi-dazy, according to others — from the NADN-oxidase or NADFN-tsito-hrom reductases, located in the same structures, as tiroido-peroksidazny system.
of Tiroidoperoksidaznaya system has no special specificity in comparison with miyelo-or lactobrace bits-sidaznymi systems on the ability to catalyze a yodination of a tiroglobulin and to form T4 and T3. Yodtironina, including T4 and T3, P. of granulocytes, acinous cells of salivary and mammary glands, a mucous membrane of a uterus are formed. But advantage of tiroidoperok-sidazny system in comparison with others consists in its bigger efficiency of a yodination at low concentration of the activated iodine.
Thus, from the known three types of peroxide of zny systems two carry out all three functions: antimicrobic, digestive (due to oxidizing deamination and decarboxylation of amino acids) and metabolic. The Tiroidoperoksidazny system is more specialized and intended for performance of one important function — synthesis of hormones of a thyroid gland. It is also necessary to emphasize that only three types of peroksidazny systems P are studied still most in detail. In nek-ry types of cells the system of an ovoperoksidaz — hydrogen peroxide — a haloid cofactor is known, edges in P. of ova of a sea hedgehog it is localized in one of groups of the cortical granules containing also mucopolysaccharides and nelizo-somny acid hydrolases. With receipt of an incentive (fertilization or parthenogenetic activation) there is a flash of oxidizing activity to intensive generation of hydrogen peroxide. This system participates in formation of a dense membrane of an ovum and has spermicidal effect (similarly to P. of eosinophils and an epithelium of a mucous membrane of a uterus), blocking a polyspermia.
By analogy with lysosomic diseases it is possible speak about pathology P. Patogenez of peroksidazosom-ny diseases can be connected with deficit or total absence of enzymes (peroxidases), disturbance of work of enzymatic systems of generation of a perekrgsa of hydrogen, deficit of the oxidized cofactors of peroksidazny systems or with their inability to get into a cell and its P., with defect of a membrane of P., etc. Such classification is considerably schematical as various combinations of the specified defects meet more often. Diseases with disturbance of activity of miyeloperoksidazny systems are well studied.
At their hereditary deficit anti-fungal activity of neutrophils is sharply broken, and also their activity in relation to other microorganisms, napr, to golden staphylococcus and colibacillus decreases. The diseases connected with hereditary deficit of myeloperoxidases proceed is rather good-quality (in the absence of additional diseases, napr, a diabetes mellitus when sensitivity of the patient to infections sharply increases). However the acquired decrease of the activity or total disappearance of myeloperoxidase is characterized extremely heavy a wedge, a current, though in these cases a certain bactericidal activity remains due to antimicrobic effect of the generated hydrogen peroxide and cationic proteins, and also due to preservation of antimicrobic activity in eosinophils and basophiles. At leukemia not only deficit of myeloperoxidase, but also the lowered P.'s number and their raised autophagy of l of isosom mi neutrophils is noted. Very high sensitivity of such patients to infections is well-known, but also in this case certain functional compensation for the account of presence of neutrophils from a normal clone of stem cells of marrow is possible (see the Hemopoiesis).
Also other anomalies of P. Izvestno total absence of tiroido-peroxidase are described at an inborn hypothyroidism (see) with total absence of a yodination of a tiroglobulin. At patients with dysfunction of a thyroid gland instability of a tiroidoperoksid heat of system, perhaps, because of inability of the activated iodine to connect to tiroidoperoksidazy and to give it stability is supposed. One of a serious hereditary illness is connected with disturbance of euzymatic system of generation of hydrogen peroxide in P. of neutrophils and mononuklear and it is known as children's hron. granulomatosis. This disease can be shown by a lymphadenopathy, a gepatosplenomegaliya, osteomyelitis, a stomacace, abscesses of a liver, dermatitis, suppuration limf, nodes, persistent rhinitis and conjunctivitis, pneumonia, etc. (sick children die despite an intensive care antibiotics). Because of defect in euzymatic system of generation of hydrogen peroxide when its giving completely stops, work of myeloperoxidases is broken - ache systems P. of neutrophils, monocytes and macrophages. Are known nek-ry patol. the states connected with the oxidized cofactors of peroksidazny systems. Inability of the activated iodine to get into tissue of a thyroid gland because of poor supply of peroxidases - ache systems a haloid component clinically it is shown by a hypothyroidism.
The general anomaly of P. of neutrophils and eosinophils is noted at a so-called periodic disease (see), the cut is a characteristic sign imitation of an aseptic inflammation of serous covers. The pathogeny is connected with abnormal periodic secretion of contents of P. of granulocytes in a serous cavity, and inflammatory process is caused by the components P cosecreted at the same time. Allocation of diseases of P. allows to define a pathogeny of a number of diseases at the level of organellas.
It is useful to consider P.'s existence by search of new medicinal connections, to-rye can increase bacterial action of neutrophils due to increase in volume or P. Uzhe's activity connection Clofibratum (gipolipoproteinemiche-sky means) is found, to-ry at oral administration increases P.'s volume in neutrophils of mice twice.
The important investigations follow from the fact of existence of special antimicrobic organellas of P., other than lysosomes: peroksidazosoderzhashchy leukocytic granules cannot be an object for studying of lysosomes and do not perform their function; lysosomes have no antimicrobic activity because all results on a research of bactericidal activity of lysosomes are received on leukocytic «lysosomes» and are unreasonably extended to true lysosomes; not lysosomic acid hydrolases of secretory granules do not function neither in a secretory granule, nor in a phagosoma, nor outside a cell.
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