Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Normal human neutrophils triggered by precipitating immune complexes (IC), soluble IC (sIC) or heat-aggregated IgG (HAIgG) displayed low levels of cytotoxicity towards nonsensitized target cells. Catalase, but not heated catalase, completely impaired this nonspecific cytotoxicity (NSC), suggesting a key role for hydrogen peroxide (H2O2) in the lysis of target cells. Superoxide dismutase (SOD) and certain HO. and 1O2 scavengers were unable to exert significant effects. Three haem-enzyme inhibitors, sodium azide, sodium cyanide and 3-amino-1,2,4-triazole did not decrease neutrophil NSC, but markedly enhanced it. This data suggest that the mechanism involved was not dependent upon myeloperoxidase (MPO). The analysis of neutrophil-mediated ADCC indicates that oxygen-dependent but MPO-independent mechanisms appeared to be operative in this system. It was also found that the microfilament disrupting agents, cytochalasin B (CB) and dihydrocytochalasin B (dhCB), as well as the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), significantly enhanced NSC. In contrast, these compounds partially inhibited ADCC. This cytotoxic system provides a suitable model to study events that may occur during the course of immune complex diseases and also permits the evaluation of alternative lytic mechanisms triggered through neutrophil Fc gamma receptors.
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PMID:Neutrophil-mediated cytotoxicity triggered by immune complexes: the role of reactive oxygen metabolites. 282 3

Normal human monocytes were induced to lyse nonsensitized target cells when triggered by precipitating immune complexes (IC) or soluble heat-aggregated IgG (HAIgG). Catalase, azide, cyanide and three aminoacids employed as quenchers of ClO, significantly inhibited this nonspecific cytotoxicity (NSC), suggesting an important role for the myeloperoxidase (MPO) system. However, HO and/or 1O2 may also be involved in the lysis, since certain scavengers of these species such as mannitol, benzoate, ethanol and histidine, as well as superoxide dismutase (SOD), partially inhibited NSC. Moreover, cyanide and azide were unable to completely abrogate this lytic activity. When NSC was compared to antibody dependent cellular cytotoxicity (ADCC), it was found that neither catalase nor oxygen-species scavengers affected ADCC while azide and cyanide significantly enhanced it. Antibody-coated target cells were also destroyed by IC-triggered monocytes. However, kinetic analysis and studies on the capacity of catalase to inhibit the lysis demonstrated that it was mediated through a NSC-like mechanism. The cytotoxic system described in this report offers a suitable model to study in vitro alternative lytic mechanisms triggered through monocyte receptors for the Fc portion of IgG (Fc gamma R).
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PMID:The role of reactive oxygen intermediates in nonspecific monocyte cytotoxicity induced by immune complexes. 303 42