Enzymes of oxidative metabolism in the human eosinophil.
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Catalase↗
Biomedical subjects
D A Bass
Publications and source records attributed to D A Bass.
Independent stimulation of motility and the oxidative metabolic burst of human polymorphonuclear leukocytes.
It has recently been suggested that a single stimulus to the membrane of the polymorphonuclear neutrophil leukocyte (PMN) produces a sequential, stereotyped response involving motility, degranulation, and the oxidative metabolic burst, and conversely, that the chemotactic response is dependent upon the stimulation of the hexose monophosphate shunt (HMPS). We have used small, synthetic substances, known to cause either increased motility or the metabolic burst, to examine whether these events can be stimulated independently. Phorbol myristate acetate (PMA) is a surface active agent that causes marked stimulation of iodination, superoxide production, chemiluminescence, and the HMPS. Such stimulation by PMA did not alter random or directional motility of PMN in the chemotaxis-under-agarose assay. Also, preincubation of PMN with PMA did not deplete their energy source for chemotaxis as demonstrated by a normal chemotactic response to zymosan activated serum. N-formylmethionyl peptides (f-met-phe, f-met-leu-phe) caused a dose-related stimulation of random and directional motility of PMN, but only a very slight stimulation of the HMPS, protein iodination, superoxide production, or chemiluminescence, and this minimal response occurred at more than 1000 times the concentration needed for stimulation of motility. These results indicate that stimulation of motility in the metabolic burst may involve separate events at the membrane of the PMN and that the events are not necessarily interdependent.
Chemotaxis, Leukocyte↗
Human eosinophilic peroxidase: role in bactericidal activity.
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Alanine↗
Comparison of intracellular bactericidal activities of human neutrophils and eosinophils.
Eosinophils from a patient with hypereosinophilia were observed to phagocytize radiolabeled E. coli or S. aureus as effectively as neutrophils from a normal control. This was observed at a number of bacteria/cell ratios and a various time intervals following initial challenge and was confirmed by direct microscopic examination. In spite of comparables rates of phagocytosis, the eosinophils were consistently less capable of killing the bacteria. This correlates with an inability of eosinophil peroxidase to catalyze the peroxidase-H2O2-CI--mediated decarboxylation of amino acids; in contrast, both eosinophil and neutrophil peroxidases showed similar capabilities to iodinate protein in vitro. These data are compatible with the importance of the chloride-mediated mechanism in the bactericidal activity of intact phagocytes.
Blood Bactericidal Activity↗
Reproduction of the eosinopenia of acute infection by passive transfer of a material obtained from inflammatory exudate.
Studies of the eosinopenic effect of acute inflammation were conducted in mice previously rendered eosinophilic with trichinosis. Exudate removed from a pneumococcal abscess contained material (eosinopenic factor [EF]) capable of causing eosinopenia of 4- to 24-h duration when injected intraperitoneally into eosinophilic mice. The material passed through a 0.45-micronm filter, but was retained by a dialysis membrane capable of retaining protein molecules of greater than approximately 30,000 molecular weight. EF was soluble in 7% perchloric acid, was not destroyed by pneumococcal proteolytic enzymes in the presence of Trasylol, but was inactivated by heating to 56 degrees C for 30 min. EF was detectable in the exudate after 10 h and had reached its highest concentration after 20 h. When the effect of EF was expressed as a percent suppression of control eosinophil levels, there was a geometric dose response. Eosinopenia could not be ascribed to steroids present in the preparation, and the EF was effective in adrenalectomized animals. Eosinopenia was not induced by transfer of similarly treated heat-killed pneumococci, pneumococcal culture filtrate, or normal serum. The eosinopenia of acute infection may be the direct effect of a substance present at the site of acute inflammation.
Adrenalectomy↗
Polymorphonuclear leukocyte bactericidal activity and oxidative metabolism during glutathione peroxidase deficiency.
Glutathione peroxidase (GPx) deficiency has been proposed as a cause of some instances of chronic granulomatous disease (CGD). GPx activity varies greatly among species, and specific deficiency of this selenium-dependent enzyme can be produced by dietary selenium deficiency in rats. Bactericidal activity of polymorphonuclear (PMN) leukocytes from normal rats, humans, and guinea pigs (GPx high, intermediate, and nearly absent, respectively), selenium-deficient rats (GPx absent), and a patient with CGD were compared. There was no correlation between natural levels of GPx and bactericidal activity; only CGD was associated with inability to kill a Proteus mirabilis strain in vitro (killing known to be dependent on oxidative mechanisms). Postphagocytic metabolism was examined in normal and GPx-deficient rats. Both demonstrated normal iodination and superoxide production during phagocytosis and gave similar histochemical reduction of nitroblue tetrazolium dye under either resting or endotoxin-stimulation conditions. Postphagocytic hexose monophosphate shunt activity was somewhat lower in PMN from GPx-deficient animals as compared with normal but was substantially (10-fold) higher than that observed in resting cells. Thus, postphagocytic oxidative responses and subsequent bactericidal activity of PMN leukocytes were not compromised by complete absence of GPx, even in the species with the highest natural level of this enzyme. These results are not compatible with the hypothesis that CGD can be caused by a deficiency of GPx.
Animals↗
The eosinophil.
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Adrenal Cortex Hormones↗
Oxidative metabolism of the human eosinophil.
We have compared the oxidative metabolism of human eosinophils (80%-90% purity) to that of neutrophils. Hexose monophosphate (HMP) shunt activity of eosinophils was higher than that of neutrophils under either resting or phagocytizing conditions. Eosinophil HMP shunt activity also was stimulated by phorbol myristate acetate, a membrane-active agent. Eosinophils showed a marked incorporation of 125I into trichloroacetic acid-insoluble material under resting conditions, which increased markedly during phagocytosis. Eosinophils likewise showed a greater reduction of nitroblue tetrazolium dye during phagocytosis than did neutrophils. Measurement of other parameters of oxidative metabolism indicated that eosinophils generated superoxide anion following phagocytosis and also elicited a burst of chemiluminescence similar to that observed during phagocytosis by neutrophils. Measurement of NADPH oxidase activity demonstrated that this enzyme was 3-6 times more active in fractions isolated from eosinophils than in corresponding fractions isolated from neutrophils; this was observed over a range of substrate concentrations. The eosinophil enzyme sedimented differently than the neutrophil enzyme with differential centrifugation; neither showed sedimentation characteristics of peroxidase. These data indicate that eosinophils possess a similar, although in some ways more potent, oxidative burst than neutrophils and are consistent with a role for NADPH oxidase in the initiation of that burst.
Asthma↗
Behavior of eosinophil leukocytes in acute inflammation. I. Lack of dependence on adrenal function.
Acute infection is accompanied by a characteristic reduction in circulating eosinophils. This study examined the generally held assumption that the eosinopenia of infection is a manifestation of adrenal stimulation. Trichinosis, Escherichia coli pyelonephritis, and early subcutaneous pneumococcal abscess were used as experimental infections of limited severity. Trichinosis is associated with eosinophilia, but pyelonephritis and pneumococcal infection produce eosinopenia. An assay for serum corticosterone was developed that is sufficiently sensitive to be performed with the small volumes of blood obtained sequentially from individual mice. The corticosterone response to trichinosis fits the sterotyped reaction previously reported for several other bacterial, viral, and rickettsial infections. The peak concentrations of corticosterone in serum from mice with trichinosis was approximately twice normal and occurred at the onset of clinical illness. Serum corticosterone levels gradually declined to the normal range over the next several days. E. coli pyelonephritis produced a similar adrenal response, although the peak serum corticosterone caused by pyelonephritis was less than the serum corticosterone occurring during the first peak of eosinophilia during trichinosis. Infection of a subcutaneous air pouch with penumococci produced eosinopenia within 6 h after inoculation, but there was no rise in serum corticosterone during the first 12 h of the pneumococcal infection. In addition, the eosinopenic response produced by a 12-hpneumococcal abscess occurred mice adrenalectomized 1-4 days before infection with pneumococci. The eosinopenia of acute infection cannot be ascribed to adrenal stimulation.
Adrenal Cortex Hormones↗
Behavior of eosinophil leukocytes in acute inflammation. II. Eosinophil dynamics during acute inflammation.
The marked diminution in the number of circulating eosinophils, which has been shown to occur during acute bacterial infections, is a distinctive aspect of eosinophil physiology and of the host response to acute infection. The mouse rendered eosinophilic by infection with trichinosis provides a suitable model for study of the eosinopenic response induced by acute inflammation. The alterations in eosinophil dynamics associated with acute inflammatory reactions in trichinous mice were studied with pneumococcal abscesses, with Escherichia coli pyelonephritis, with Coxsackie viral pancreatitis, and with acute subcutaneous inflammation due to turpentine. Each of these stimuli of acute inflammation markedly suppressed the eosinophilia of trichinosis. This suggests that the eosinopenia is a response to the acute inflammatory process rather than the response to a specific type of pathogen. These studies apply quantitative techniques to ascertain the effects of acute inflammation on eosinophil production in bone marrow and on distribution of eosinophils in the peripheral tissues. From these observations, it is apparent that the initial response to acute inflammation includes a rapid drop in numbers of circulating eosinophils, a rapid accumulation of eosinophils at the periphery of the inflammatory site, and an inhibition of egress of eosinophils from the bone marrow. With prolongation of the inflammatory process, inhibition of eosinopoiesis occurs.
Acute Disease↗
Mechanism of eosinophilia. X. Evidence for immunologic specificity of the stimulus.
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Animals↗
Regulation and metabolism of arachidonic acid.
The metabolism of AA reflects a carefully balanced series of biochemical pathways. The level of free arachidonate in a cells is controlled by de novo synthesis, dietary uptake, and transcellular metabolism. Lysophospholipids are key controlling substrates for a variety of acyl transferase and transacylase reactions, whose combined effect is to remodel cellular membranes placing AA in up to 20 different molecular species of phospholipids. PLA2 enzymes, both cytosolic and secretory, can release AA for subsequent metabolism via lipoxygenase, COX, and cytochrome P450 enzymes into a variety of eicosanoid products. Reactions are often tissue- and cell-specific, and provide a spectrum of inflammatory mediator release in which many of the molecular details remain to be elucidated.
Animals↗