Serine protease inhibitors inhibit superoxide production by human polymorphonuclear leukocytes and monocytes stimulated by various surface active agents

Kitagawa, Seiichi; Takaku, Fumimaro; Sakamoto, Shinobu

doi:10.1016/0014-5793(79)80401-9

Cited by 35 publications

(9 citation statements)

References 11 publications

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“…Cytochrome C reduction by cells stimulated by these surface active agents was completely abolished by superoxide dismutase (40Mg/ml), and suggested to be specific for O°. The production of°2 was calculated from cytochrome C reduced for 3 min after the addition ofFMLP or A23 187, and from the linear portion of cytochrome C reduction for PMA (12).…”

Section: Methodsmentioning

confidence: 99%

Functional maturation of membrane potential changes and superoxide-producing capacity during differentiation of human granulocytes.

Kitagawa¹,

Ohta²,

Nojiri³

et al. 1984

J. Clin. Invest.

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Abstract. The alterations of stimulus-induced membrane potential changes, superoxide (O°)-producing capacity and phagocytic activity during differentiation of human granulocytes were investigated in the human leukemia cell lines HL-60 and KG-1 differentiating in vitro and in human leukemic granulocytes obtained from chronic myelogenous leukemia patients. HL-60 cells incubated with dimethyl sulfoxide or with retinoic acid showed progressively increasing O2 production as well as membrane potential changes (depolarization) on contact with phorbol myristate acetate or the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine, with a concomitant increase in the proportion of mature cells of the granulocytic type. Phagocytosis oflatex particles, yeast, and oil droplets appeared 24 h after incubation with dimethyl sulfoxide and anteceded the increment of02 production and membrane potential changes, both of which appeared concomitantly 3 d after incubation with dimethyl sulfoxide. Similar findings were observed when immature and mature granulocytes obtained from chronic myelogenous leukemia patients were stimulated by phorbol ester, the chemotactic peptide, or calcium ionophore A23 187, and the amount of 0°production was parallel to the magnitude of membrane potential changes. HL-60 and KG-1 cells incubated for 1-6 d with phorbol Address correspondence to Dr. Kitagawa, Department of Pediatrics, National Jewish Hospital and Research Center, University of Colorado School of Medicine, Denver, CO 80206 (until August 1985).Received for publication 19 April 1983 and in revised form 22 December 1983. myristate acetate showed neither 0°production nor membrane potential changes on contact with phorbol ester, chemotactic peptide, or A23187, although such cells resembled macrophages morphologically, and their phagocytic activity was significantly increased. 02-production and membrane potential changes in normal granulocytes induced by phorbol ester, chemotactic peptide and A23 187 were inhibited by 2-deoxyglucose. These findings indicate that the 0--producing system and the system provoking membrane potential changes may develop concomitantly as human granulocytes mature and differentiate, and that the development of these systems and of phagocytic activity may be independently regulated.

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Section: Methodsmentioning

confidence: 99%

Functional maturation of membrane potential changes and superoxide-producing capacity during differentiation of human granulocytes.

Kitagawa¹,

Ohta²,

Nojiri³

et al. 1984

J. Clin. Invest.

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“…Suppression was reduced or absent when PBMC were depleted of adherent cells, implicating monocytes in the suppression of NK (24). Other investigators have shown that TPA stimulates monocytes and polymorphonuclear leukocytes (PMN) to release reactive metabolites of molecular oxygen (RO), including superoxide anion (O°), hydrogen peroxide (H202), hydroxyl radical (OH *), and singlet oxygen ('02) (25)(26)(27)(28).…”

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confidence: 99%

“…The stimulated rate of cytochrome C reduction was corrected for the resting rate or the non-SOD-inhibitable rate. The increase in A550 was converted to nanomolar ferricytochrome C by using a molar extinction coefficient of 21 (25)(26)(27)(28), we examined the effects of serum-opsonized zymosan, an unrelated agent that also stimulates the release of RO (27,34). NK was reduced when opsonized zymosan was present during the cytotoxicity assay.…”

mentioning

confidence: 99%

Suppression of natural killing in vitro by monocytes and polymorphonuclear leukocytes: requirement for reactive metabolites of oxygen.

Seaman¹,

Gindhart²,

Blackman³

et al. 1982

J. Clin. Invest.

121

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A B S T R A C T Natural killer cells spontaneously lyse certain tumor cells and may defend against malignancy. We have previously shown that natural killing (NK) by human peripheral blood mononuclear cells (PBMC) is suppressed in vitro by phorbol diester tumor promoters, including 12-0-tetradecanoylphorbol-13-acetate (TPA). We here demonstrate that suppression of NK is mediated by monocytes or polymorphonuclear leukocytes (PMN) and that suppression is dependent on the generation of reactive forms of molecular oxygen (RO), particularly hydrogen peroxide (H202). NK was suppressed not only by TPA but also by opsonized zymosan (yeast cell walls), which, like TPA, was not toxic to PBMC. Both TPA and zymosan stimulated the production of superoxide anion (O°) and H202 by PBMC. Production of RO correlated with suppression of NK. When PBMC were depleted of monocytes, the production of RO and the suppression of NK were both markedly reduced. Suppression could be restored by monocytes or PMN, both of which produced RO Suppression of NK by TPA was inhibited by catalase. Bovine superoxide dismutase had a limited effect on suppression, even in high concentration, and tyrosinecopper (II) complex, which also enhances dismutation of°2 to H202, had almost no effect on suppression.When H202 was directly generated enzymatically from glucose oxidase and glucose, NK was suppressed and suppression was reversed by catalase. NK was also suppressed by the enzymatic generation of°2 from xanthine oxidase and xanthine, but suppression under these conditions was again inhibited by catalase and not by superoxide dismutase, indicating that suppression was due to the secondary formation of H202 from O°. These results indicate that H202 is important in suppression of NK. Myeloperoxidase did not appear to play a role in suppression because inhibition of this enzyme by sodium azide, cyanide, or aminotriazole did not prevent suppression of NK. Suppression of NK was reversible; after exposure to zymosan, NK could be partially restored by the addition of catalase and superoxide dismutase or by the removal of zymosan. These studies demonstrate cellular regulation of NK by monocytes or polymorphonuclear leukocytes and indicate a role for RO in immunoregulation. INTRODUCTION Natural killer cells are mononuclear cells that spon-

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“…In particular, agents like the aminoacyl chloromethanes N"-ptosyl-r>-phenylalanyl chloromethane (TosPheCH,Cl) and Nup-tosyl-L-lysyl chloromethane (TosLysCH,CI) were always found to inhibit the respiratory burst, when the cell stimulus was PMA [29-351, Met-Leu-Phe [29,32,36,371, opsonized zymosan [35], cytochalasin E plus concanavalin A [35,[38][39][40], immune complexes [40, 411, arachidonate [35] or SDS [40]. More recently, carbobenzoxy-leucyl-tyrosyl chloromethane (zLeuTyrCH,CI) was found to inhibit the respiratory burst elicited by Met-Leu-Phe, but not that triggered by PMA [42,431.…”

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confidence: 99%

Aminoacyl chloromethanes as tools to study the requirements of NADPH oxidase activation in human neutrophils

Chollet-Przednowed

Lederer

1993

European Journal of Biochemistry

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Previous studies from this laboratory described the kinetic characteristics of the inhibition by tosylphenylalanine chloromethane (TosPheCH,Cl) on superoxide anion production by human neutrophils (PMN) stimulated with a phorbol ester (PMA). In this study we present further evidence concerning the potential role of the chloromethane target in the normal cellular activation of NADPH oxidase. When PMN are treated with TosPheCH,Cl and subsequently PMA, or with the two reagents in the reverse order, the inhibition of superoxide production by the intact cells is still present in a particulate NADPH oxidase fraction prepared from these cells. Nevertheless, when cells incubated only with the chloromethane and not with PMA are disrupted, both their cytosolic and membrane fractions are fully competent in the cell-free activation assay. Thus, the chloromethane target has a role in NADPH oxidase activation exclusively at the cellular level. This observation constitutes additional evidence in favour of the idea that activation in the cell-free system reflects only partially the events which occur in the cells.When cells are activated with PMA, their cytosol displays a loss of activating capacity in the cell-free activation assay in the presence of arachidonate, as was shown before with SDS as activatorBiol. Chem. 265,924-9301. This phenomenon was shown to arise most probably from the translocation of cytosolic factors to the membrane, resulting in a depleted cytosol. When superoxide production was inhibited by cell treatment with TosPheCH,Cl, either before or after activation with PMA, the cytosol from inhibited cells showed a recovery of activation capacity in the cell-free system. This effect probably results from TosPheCH,Cl inhibiting the translocation of the cytosolic factors when added before PMA. This results in an insufficient activation at the membrane level, which was previously considered as an inhibition. The effect of TosPheCH,Cl, when added after PMA, can best be explained again as an inhibition of translocation in the frame of the continuous replenishment In this study, we have also found that [3H]TosPheCH,C1-labeled cells show a prominent radiolabeled band of M, 15000 after SDSPAGE analysis of the cytosolic proteins from inhibited cells; this species has the same migration as the labeled membrane protein detected previously, but appears much more abundant on a proteidcell basis. The potential role of the TosPheCH,Cl protein target is discussed.Polymorphonuclear leukocytes (PMN) constitute the first line of defense against infection in higher organisms. Contact between bacteria o r other pathogens and PMN induces phagocytosis and destruction of the invader cells in the phagolysosomes. An important element of this defense mechanism is constituted by the toxic oxygen derivatives generated as the result of superoxide anion production by NADPH oxidase, an enzyme system which is activated upon cell stimulation [l-31.The best identified redox component of NADPH oxidase, a plasma-membrane bound complex, is the hetero...

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Serine protease inhibitors inhibit superoxide production by human polymorphonuclear leukocytes and monocytes stimulated by various surface active agents

Cited by 35 publications

References 11 publications

Functional maturation of membrane potential changes and superoxide-producing capacity during differentiation of human granulocytes.

Functional maturation of membrane potential changes and superoxide-producing capacity during differentiation of human granulocytes.

Suppression of natural killing in vitro by monocytes and polymorphonuclear leukocytes: requirement for reactive metabolites of oxygen.

Aminoacyl chloromethanes as tools to study the requirements of NADPH oxidase activation in human neutrophils

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