Reactions of oxygen radical species with methional: A pulse radiolysis study

Bors, Wolf; Lengfelder, Edmund; Sarán, Manfred; Fuchs, Christine; Michel, Christa

doi:10.1016/0006-291x(76)91111-6

Cited by 43 publications

(10 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…in PMNs (12,13) and monocytes (14) has been proposed based on the formation of ethylene from ~-methylthiopropionaldehyde (methional) or 2-keto-4-thiomethylbutyric acid (KMB), a reaction which can occur by an OH. mechanism (6,15). In this paper, ethylene formation by intact PMNs is shown to be largely dependent on MPO, and a cellfree, SOD-sensitive, MPO-dependent system with properties similar to those of the intact cell is described.…”

mentioning

confidence: 83%

Ethylene formation by polymorphonuclear leukocytes. Role of myeloperoxidase.

Klebanoff¹,

Rosen²

1978

The Journal of Experimental Medicine

116

View full text Add to dashboard Cite

Micro-organisms ingested by polyrnorphonuclear leukocytes (PMNs) I are exposed to a variety of anti-microbial systems; some require oxygen, whereas others are effective under anaerobic conditions (1, 2). The importance of the oxygen-dependent anti-microbial systems is emphasized by the presence of a major microbicidal defect associated with an impairment in the phagocytosis-induced respiratory burst in the PMNs of patients with chronic granulomatous disease (CGD). One of the oxygen-dependent anti-microbial systems of the PMN consists of myeloperoxidase (MPO), H2Os, and a halide. After phagocytosis, MPO is released into the phagocytic vacuole from adjacent lysosomal granules where it interacts with H202 generated either by leukocytic or microbial metabolism and a halide such as chloride or iodide to form an agent or agents toxic to the ingested organisms. The evidence in support of a role for the MPO-mediated anti-microbial system in the microbicidal activity of the intact cell is substantial (I, 2). Of particular pertinence is the finding of a major fungicidal and bactericidal defect in leukocytes which lack MPO, i.e., from patients with hereditary MPO deficiency (3, 4).Oxygen-dependent anti-microbial agents which do not require MPO also are present in the PMN; among these may be the hydroxyl radical (OH.), generated by the interaction of the superoxide anion (O~-) and H202. The superoxide anion is formed by the univalent reduction of oxygen and its dismutation to form H202 readily occurs either spontaneously or catalyzed by superoxide dismutase (SOD). A mechanism for the formation of OH-was proposed by Haber and Weiss (5):Of-+ H202 ~ OH. + OH-+ 02. (a)When a chemical reaction is induced by a Of-H2()2 generating system, the inhibition of that reaction by SOD, catalase, and OH. scavengers such as mannitol, ethanol, and benzoate and its stimulation by H202, have been employed as evidence for the involvement of OH-generated by the Haber-Weiss reaction (6). The Haber-Weiss reaction has recently been questioned as an efficient mechanism for the generation of OH. (7, 8); however a number of reactions respond to inhibitors in a manner suggestive of the participation of O~-, H202 and OH., leaving open the possibility that OH. is generated by an, as yet, unknown mechanism requiring O~-and H202.Both O~-(9) and H202 (10) are generated by PMNs during phagocytosis and the formation of OH. by phagocytosing PMNs might therefore be anticipated. * Supported in part by grants AI07763 and CA18354 from the U. S. Public Health Service.Abbreviations used in this paper: CGD, chronic granulomatous disease; DABCO, 1,4-diazabicyclo [2,2,2] octane; D20, deuterium oxide; KMB, 2-kete-4-thiomethylbutyric acid; MPO, myeloperoxidase; O~ -, superoxide anion; 102, singlet oxygen; OH., hydroxyl radical; PMN, polymorphonuclear leukocyte; SOD, superoxide dismutase. 490J. Exp. MED.

show abstract

mentioning

confidence: 83%

Ethylene formation by polymorphonuclear leukocytes. Role of myeloperoxidase.

Klebanoff¹,

Rosen²

1978

The Journal of Experimental Medicine

116

View full text Add to dashboard Cite

show abstract

“…However, it is possible that other radicals interact with KMB.°2 reacts weakly with methional (29), and perhaps it may react with KMB, a related compound. Klebanoff and Rosen have raised the possibility that ethylene production from KMB in the MPO H202-halide system may be the result of singlet oxygen, not OH (8).…”

Section: Methodsmentioning

confidence: 99%

Lactoferrin enhances hydroxyl radical production by human neutrophils, neutrophil particulate fractions, and an enzymatic generating system.

Ambruso¹,

Johnston²

1981

J. Clin. Invest.

320

111

View full text Add to dashboard Cite

A B S T R A C T During phagocytosis, neutrophils take oxygen from the surrounding medium and convert it to superoxide anion (O°) and hydrogen peroxide (H202). Hydroxyl radical ( OH), a particularly potent oxidant, is believed to be produced by interaction between O2 and H202 in the presence of iron, according to the Haber-Weiss reactions. Production of OH by whole human neutrophils, by particulate fractions from human neutrophils disrupted after stimulation, and by a xanthine oxidase system was measured by conversion of a-keto-y-methiol butyric acid to ethylene. FeCl3 or ferric EDTA enhanced ethylene production in all three systems by 155-406% of base line at a concentration of 50-100 ,uM. Iron-saturated human milk lactoferrin, 100 nM, increased ethylene generation by 127-296%; and purified human neutrophil lactoferrin, 10 nM, enhanced ethylene production by 167-369%. Thus, iron bound to lactoferrin was -5,000 times more effective in producing an enhancement in ethylene generation than iron derived from FeCl3 or ferric EDTA. 02 and H202 were required for ethylene production in the presence of lactoferrin, since superoxide dismutase inhibited ethylene formation in the three systems by 76-97% and catalase inhibited by 76-98%. Ethylene production in the presence of lactoferrin was inhibited by the OH scavengers mannitol, benzoate, and thiourea by , and 76-96%, respectively. Thus, most of the ethylene production could be attributed to oxidation of a-keto-y-methiol butyric acid by OH. The ability ofneutrophil lactoferrin to provide iron efficiently to the oxygen radical-generating systems is compatible with a role for lactoferrin as regu-

show abstract

“…Hypoxanthine (7) and ethylene production from a-keto-'y-methiolbutyric acid (KMB) (20,21). Although none of these reactions appears to be entirely specific (16,22), when the reactants are H202, superoxide and Fe(EDTA), the evidence is strongly in support of the hydroxyl radical being the reactive species (7,16 Myeloperoxidase was purified from human neutrophil granules (24). The A^3/A280 ratio was 0.73 and its concentration was calculated using E43 = 91,000 M-' cm-' (with respect to iron).…”

Section: Introductionmentioning

confidence: 99%

Myeloperoxidase as an effective inhibitor of hydroxyl radical production. Implications for the oxidative reactions of neutrophils.

Winterbourn¹

1986

J. Clin. Invest.

107

View full text Add to dashboard Cite

Hydroxyl radicals have been generated from hydrogen peroxide and superoxide (produced with xanthine oxidase), and an iron (EDTA) catalyst, and detected with deoxyribose, or in some cases with benzoate or a-keto-'y-methiolbutyric acid. Purified myeloperoxidase, and neutrophils stimulated with fMet-Leu-Phe and cytochalasin B, strongly inhibited this hydroxyl radical production in a concentration-dependent manner. Supernatants from stimulated cells also inhibited, and inhibition by cells or supernatant was prevented by azide. There was much less inhibition by myeloperoxidase-deficient neutrophils. Inhibition thus was due to myeloperoxidase released by the cells. With neutrophils stimulated with phorbol myristate acetate, which release very little myeloperoxidase, hydroxyl radical production was enhanced due to the additional superoxide produced by the cells. It is concluded that under conditions where neutrophils release myeloperoxidase as well as superoxide and hydrogen peroxide, breakdown of hydrogen peroxide by myeloperoxidase would make conditions unfavorable for hydroxyl radical production.

show abstract

Reactions of oxygen radical species with methional: A pulse radiolysis study

Cited by 43 publications

References 17 publications

Ethylene formation by polymorphonuclear leukocytes. Role of myeloperoxidase.

Ethylene formation by polymorphonuclear leukocytes. Role of myeloperoxidase.

Lactoferrin enhances hydroxyl radical production by human neutrophils, neutrophil particulate fractions, and an enzymatic generating system.

Myeloperoxidase as an effective inhibitor of hydroxyl radical production. Implications for the oxidative reactions of neutrophils.

Contact Info

Product

Resources

About