Role of oxygen in antibody-dependent cytotoxicity mediated by monocytes and neutrophils.

Borregaard, Niels; Kragballe, Knud

doi:10.1172/jci109904

Cited by 80 publications

(27 citation statements)

References 21 publications

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“…Indeed, MPO-deficient granulocytes successfully destroyed both erythrocyte3 and endothelial cell targets (23). Recent reports have also demonstrated that human monocytes and neutrophils can destroy target cells in antibody dependent (14,(50)(51)(52) or serum independent systems (53 …”

Section: Discussionmentioning

confidence: 99%

Monocyte and granulocyte-mediated tumor cell destruction. A role for the hydrogen peroxide-myeloperoxidase-chloride system.

Weiss¹,

Slivka

1982

J. Clin. Invest.

149

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A B ST R A CT Human monocytes stimulated with phorbol myristate acetate were able to destroy a T lymphoblast cell target (CEM). Stimulated human granulocytes were also capable of mediating CEM cytotoxicity to a comparable degree as the monocyte. CEM destruction was dependent on the pH and the effector cell number. Both monocyte or granulocyte mediated cytotoxicity were inhibited by the addition of catalase, whereas superoxide dismutase had no inhibitory effect. In addition, CEM were protected from cytolysis by the effector cells by the myeloperoxidase inhibitors, azide and cyanide, or by performing the experiment under halide-free conditions. Glucose oxidase, an enzyme system capable of generating hydrogen peroxide, did not mediate CEM cytotoxicity, while the addition of purified myeloperoxidase dramatically enhanced cytolysis. Hypochlorous acid scavengers prevented CEM destruction by the glucose oxidase-myeloperoxidase-chloride system but neither hydroxyl radical nor singlet oxygen scavengers had any protective effect. These hypochlorous acid scavengers were also successful in inhibiting monocyte or granulocyte-mediated CEM cytotoxicity. Based on these observations we propose that human monocytes or granulocytes can utilize the hydrogen peroxide-myeloperoxidase-chloride system to generate hypochlorous acid or a species of similar reactivity as a potential mediator of CEM destruction.

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Section: Discussionmentioning

confidence: 99%

Monocyte and granulocyte-mediated tumor cell destruction. A role for the hydrogen peroxide-myeloperoxidase-chloride system.

Weiss¹,

Slivka

1982

J. Clin. Invest.

149

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show abstract

“…24 Regarding a role of Bcl-2 proteins in this process, one should realize that PMNs are considered to possess no or only few rudimentary mitochondria, which do not play a role in the active life of the cell. 29,30 Therefore, PMNs have been considered to be "a nonmitochondrial scene" of apoptosis. 23 On the other hand, mitochondria constitute a crossroad of apoptosis regulation between members of the Bcl-2 family and the caspases.…”

Section: Introductionmentioning

confidence: 99%

Granulocyte colony-stimulating factor inhibits the mitochondria-dependent activation of caspase-3 in neutrophils

Maianski

Mul

Buul

et al. 2002

Blood

160

188

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The exact mechanism of apoptosis in neutrophils (PMNs) and the explanation for the antiapoptotic effect of granulocyte colony-stimulating factor (G-CSF) in PMNs are unclear. Using specific fluorescent mitochondrial staining, immunofluorescent confocal microscopy, Western blotting, and flow cytometry, this study found that PMNs possess an unexpectedly large number of mitochondria, which are involved in apoptosis. Spontaneous PMN apoptosis was associated with translocation of the Bcl-2-like protein Bax to the mitochondria and subsequent caspase-3 activation, but not with changes in the expression of Bax. G-CSF delayed PMN apoptosis and prevented both associated events. These G-CSF effects were inhibited by cycloheximide. The general caspase inhibitor z-Val-Ala-DL-Asp-fluoromethylketone (zVAD-fmk) prevented caspase-3 activation and apoptosis in PMNs, but not Bax redistribution. PMNderived cytoplasts, which lack a nucleus, granules, and mitochondria, spontaneously underwent caspase-3 activation and apoptosis (phosphatidylserine exposure), without Bax redistribution. zVAD-fmk inhibited both caspase-3 activation and phosphatidylserine exposure in cultured cytoplasts. Yet, G-CSF prevented neither caspase-3 activation nor apoptosis in cytoplasts, confirming the need for protein synthesis in the G-CSF effects. These data demonstrate that (at least) 2 routes regulate PMN apoptosis: one via Bax-tomitochondria translocation and a second mitochondria-independent pathway, both linked to caspase-3 activation. Moreover, G-CSF exerts its antiapoptotic effect in the first, that is, mitochondria-dependent, route and has no impact on the second.

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“…Their contribution to ADCC, however, has not been unequivocally demonstrated. A participation of reactive oxygen species had been described in lysis of antibody-coated erythrocytes, 14,15 but not for tumor cells lysis. [16][17][18] Moreover, inhibition of RNA or protein synthesis apparently did not inhibit the ADCC, 10 implying preformed mediators.…”

Section: Introductionmentioning

confidence: 99%

Granzyme B and perforin: constitutive expression in human polymorphonuclear neutrophils

Wagner

Iking‐Konert

Denefleh

et al. 2004

Blood

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Polymorphonuclear neutrophils (PMNs) produce an abundance of bactericidal and cytotoxic molecules consistent with their role as first-line defense against bacterial infection. PMNs, however, also cause efficient cellular cytotoxicity when targeted through Fc receptors to appropriate antibody-coated target cells. Although this so-called antibody-dependent cellular cytotoxicity (ADCC) was described many years ago, the mechanism of killing is still elusive. We now have found that PMNs contain perforin and granzyme B, the 2 molecules known as the cytotoxic entity of natural killer cells and of cytotoxic T lymphocytes as well. Lysates of PMNs were lytic for chicken erythrocytes in a time-, temperature-, and Ca 2؉ -dependent manner. Moreover, apoptosis of Jurkat cells was induced, consistent with the observation that the PMN lysates contain enzymatically active granzyme B. Taken together, our data provide evidence for the presence of perforin and granzyme B within the cytotoxic arsenal of PMNs.

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Role of oxygen in antibody-dependent cytotoxicity mediated by monocytes and neutrophils.

Cited by 80 publications

References 21 publications

Monocyte and granulocyte-mediated tumor cell destruction. A role for the hydrogen peroxide-myeloperoxidase-chloride system.

Monocyte and granulocyte-mediated tumor cell destruction. A role for the hydrogen peroxide-myeloperoxidase-chloride system.

Granulocyte colony-stimulating factor inhibits the mitochondria-dependent activation of caspase-3 in neutrophils

Granzyme B and perforin: constitutive expression in human polymorphonuclear neutrophils

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