Serum Factors from Patients with Systemic Lupus Erythematosus Enhancing Superoxide Generation by Normal Neutrophils

Sato, Masao; Oribe, Motohiro; Tsuruo, Takashi; Tomooka, Kazuhisa; Yasuda, Masayuki; Nobunaga, Masashi

doi:10.1111/1523-1747.ep12517989

Cited by 22 publications

(7 citation statements)

References 26 publications

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“…It is interesting that the lipid peroxide levels increased in the serum taken from MRL/l mice. Increased superoxide generation and the consequently augmented lipid peroxidation reaction play an important role in the pathogenesis of autoim mune diseases including rheumatoid arthritis and system ic lupus erythematosus (24,25). Furthermore, in MRL/l mice, the superoxide release of macrophages is remark ably elevated compared to that of macrophages in MRL/n mice (26).…”

Section: Discussionmentioning

confidence: 99%

Involvement of CGRP, Substance P and Blood Circulation in Aggravating Mechanism of Absolute Ethanol-Induced Antral Lesions by Capsaicin Treatment in Rats

Yamaguchi

Kitagawa

Imaizumi

et al. 1993

Japanese Journal of Pharmacology

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ABSTRACT-AutoimmuneMRL-lpr/lpr (MRL/l) mice, with a systemic lupus erythematosus-like disease, were shown to spontaneously develop hyperlipidemia and yet be susceptible to diet-induced hypercholes terolemia and aortic cholesterol deposition. Control animals on a basal diet showed significant increases in the serum total cholesterol, phospholipids, triglycerides, high density lipoprotein (HDL)-cholesterol and lipid peroxide levels, but a significant decline in the serum lecithin: cholesterol acyltransferase (LCAT) activ ity compared to those of 5-week-old mice. Animals on the high-cholesterol diet showed a rapid rise in serum total cholesterol to a plateau level (800 mg/ 100 ml) that was approximately 2.5 times higher than that in the control animals on a basal diet. However, the levels of serum triglycerides, HDL-cholesterol and lipid perox ides significantly decreased (by 61%, 23% and 53%, respectively) compared to those of the control animals, whereas LCAT activity and phospholipid level were not affected. The aortic contents of total cholesterol, free cholesterol and cholesteryl ester were significantly higher (by 35%, 36% and 31%, respectively) in animals fed the high-cholesterol diet than the control animals. These findings suggest that MRL/l mice are susceptible to diet-induced hypercholesterolemia and aortic cholesterol deposition.

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Section: Discussionmentioning

confidence: 99%

Involvement of CGRP, Substance P and Blood Circulation in Aggravating Mechanism of Absolute Ethanol-Induced Antral Lesions by Capsaicin Treatment in Rats

Yamaguchi

Kitagawa

Imaizumi

et al. 1993

Japanese Journal of Pharmacology

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“…Incubation time and temperature are other factors which affect the concentration required. Ncutrophiis activated by serum factors such as immune complexes or complemeni fragments in the sera from patients with SLH release Oj into extracellular fluid [43]. O; contributes to the enhancement of the inflammatory process by releasing iron fVom its bound form [40].…”

Section: Discussionmentioning

confidence: 99%

Activation of complement in normal serum by hydrogen peroxide and hydrogen peroxide-related oxygen radicals produced by activated neutrophils

Sato

Nonaka

Nishimukai

et al. 1992

Clinical and Experimental Immunology

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SUMMARYNeutrophils activated by soluble parliculate stimuli generate superoxide anion and subsequently form hydrogen peroxide and other oxygen radicals. The effect o\' hydrogen peroxide on the complement system in normal serum was investigated. Treatment of normal serum with hydrogen peroxide resulted in a diminution ofthe haemolytic activity ofthe total and alternative complement pathways and the haemolytic titres of C3 and C^ but not of C2. in normal scrum. These decreases in complcEiient aclivity depended on the conccntraiion of hydrogen peroxide added to the serum. Immunoelectrophoretic analysis of hydrogen peroxide-treated serum showed ihat C3 and C5 proteins were activated. Complemeni degradation products C3a and C5a were produced in normal serum treated with hydrogen peroxide, and 20 mM EDTA abolished C3a and C5a production in hydrogen peroxide-treated scrum but 20 mM Mg-EGTA did not, Cataiase completely abolished and dimethylsulphoxidc and t>-mannitol. hydroxyl radical scavengers, partially inhibited the hydrogen peroxide-mediated complement activation. Hypochlorite. ineubated with normal serum, significantly inhibited scrum haemolytic activity, and sodium thiosulphale. a reducing agent, abolished the effect of hypochlorite. Nonnal scrum incubaled with activated neutrophils showed neutrophil chemotactic activity and decreased serum haemolytic activity, and the addition of catalase or mcthionine (5 niM) completely abolished the elTects of activated neutrophils. These results suggest that hydrogen peroxide activates complement via an alternative pathway of complement activalion and that hydroxyl radicals and other hydrogen peroxide-related species such as hypochlorite are most likely involved in hydrogen peroxidc-mcdialcd complement activation. Complement aclivation by oxygen radicals produced by activated nentrophils may be one of the mechanisms by which complement is activated in human immune complex diseases. Keywords hydrogen peroxide hypochlorite complement aetivation neutrophils[NTRODUCTION The aclivation of the complement system by immune eomplexes via the classical pathway may be involved in initiating and sustaining the inllammatory process and subsequent tissue injury in immune complex diseases such as systemic lupus erylhematosus (SLF.) and rheumatoid arlhritis (RA), The aclivation of complement at sites of immune complex deposition in tissue plays an important role in the pathogenesis of vascular injury in such diseases. Complement fragments generated from the native complement components following aetivation of complement, arc biologically active, act as inflammatory mediators and produce tissue damage by stimulating the

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“…We also reported previously that serum ICs may stimulate PMNs to generate ROS [3]. It has been reported that increased generation of ROS may play an important role in some immune complex-mediated diseases [14,15], and that PMNs produced Table 1. ROS generation by normal rabbits' PMNs stimulated by sera from elicited rabbits.…”

Section: Discussionmentioning

confidence: 81%

Role of Reactive Oxygen Specie in Arthus Reaction

Yoshioka

Imamura

Niwa

1988

J. Clin. Biochem. Nutr.

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SummaryThe effect of serum obtained from Arthus reaction-elicited rabbits on the generation of reactive oxygen species (ROS) by normal rabbits' polymorphonuclear leukocytes (PMNs) was examined.. The oxidative metabolism of infiltrating PMNs in the skin during the Arthus reaction was observed by the nitroblue tetrazolium dye reduction test (NBT test). The significantly increased H2O2 generation by normal PMNs was observed when PMNs were incubated with serum obtained 24 and 48 h after the elicitation. Also the increased O2 -generation was noted after incubation with serum taken at 48 h after the elicitation. Many NBT-positive PMNs were observed in skin specimens obtained 24 and 48 h after the elicitation. These results may indicate the importance of ROS generated by infiltrating PMNs in immune complex vasculitis because the Arthus reaction is a model of immune complex vasculitis.Key Words: Arthus reaction, immune complex vasculitis, reactive oxygen species, skin NBT test The experimental Arthus reaction, which is a model of immune complex vasculitis, is similar to necrotizing vasculitis both macroscopically and histologically. In its pathogenesis, immune complexes (ICs) deposited on the wall of blood vessels activate the complement system with resultant production of chemotactic factors such as Coa. Then, attracted polymorphonuclear leukocytes (PMNs) produce various inflammatory mediators, and induce tissue damage in the wall of the blood vessels. These reactions are observed macroscopically as redness, induration, and bleeding, and histologically as dense infiltration of PMNs, fibrinoid degeneration of blood vessels, and nuclear dusts. In rabbits, the Arthus reaction was suppressed both macroscopically and histologically when colchicine was injected intraperitoneally before elicitation [1], indicating that PMNs play an im-*To whom correspondence should be addressed .

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Serum Factors from Patients with Systemic Lupus Erythematosus Enhancing Superoxide Generation by Normal Neutrophils

Cited by 22 publications

References 26 publications

Involvement of CGRP, Substance P and Blood Circulation in Aggravating Mechanism of Absolute Ethanol-Induced Antral Lesions by Capsaicin Treatment in Rats

Involvement of CGRP, Substance P and Blood Circulation in Aggravating Mechanism of Absolute Ethanol-Induced Antral Lesions by Capsaicin Treatment in Rats

Activation of complement in normal serum by hydrogen peroxide and hydrogen peroxide-related oxygen radicals produced by activated neutrophils

Role of Reactive Oxygen Specie in Arthus Reaction

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