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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 41 (1994), S. 101-104 
    ISSN: 1420-908X
    Keywords: Calcium toxicity ; Leukocyte ; Superoxide ; Leukotriene ; Interleukin-1β
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although calcium plays an important role in the activation of leukocytes for such processes as eicosanoid biosynthesis, secretion of granular constituents and superoxide generation, sustained high levels of intracellular calcium ions may be toxic. We have previously found that high concentrations of calcium ionophores induce a rapid-onset “calcium overload” toxicity in rat peritoneal leukocytes, in which functional responses such as β-glucuronidase secretion, superoxide generation and leukotriene B4 synthesis are greatly attenuated, and some leakage of cytoplasmic LDH occurs. We have now compared this phenomenon in peritoneal leukocytes elicited from animals pretreated in three ways: glycogen, interleukin-1β (IL-1β) alone or glycogen plus IL-1β. Peritoneal administration of IL-1β caused elicitation of cells which were enriched in eosinophils; however, the functional responses of the cells in all three groups were broadly similar in terms of the ability of the agonists FMLP, PMA and A23187 to initiate superoxide generation, β-glucuronidase secretion and leukotriene generation. Cells from all three treatment groups showed diminished responsiveness at 10−5 M A23187, indicative of calcium overload toxicity. This was most evident for the superoxide and β-glucuronidase responses. Some quantitative differences observed between treatment groups may reflect the different sensitivities of the various cells contained in the mixed leukocyte preparations. We conclude that IL-1β induces leukocyte emigration into the peritoneal cavity but that the cell population is different from that induced by glycogen. However, the cells retain susceptibility to calcium overload toxicity.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 41 (1994), S. 114-117 
    ISSN: 1420-908X
    Keywords: Labdanes ; Diterpenoids ; 5-lipoxygenase ; Cyclo-oxygenase ; Superoxide ; Reactive oxygen species ; Phospholipase A 2 ′
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two purified plant products were obtained from anti-inflammatory extracts of the Spanish herbSideritis javalambrensis: ent-13-epi-12α-acetoxy-manoyl oxide (=“manoyl oxide F1”) andent-8α-hydroxy-labda-13 (16), 14-dien (=“labdane F2”). They were evaluated for possible anti-inflammatory actionsin vitro, and were compared with aspirin, sodium salicylate and indomethacin. Neither of the natural products affected superoxide generation or scavenging and they did not affect granular enzyme secretion from activated human and rat neutrophils. The compounds were not toxic to the cells at up to 10−4 M. However, both F1 and F2 inhibited thromboxane B2 and leukotriene B4 generation by A23187-treated rat peritoneal leukocytes, suppressing leukotriene generation at 10−5 to 10−4 M and thromboxane B2 at 10−4 M. Labdane F2 also inhibited human secretory synovial phospholipase A2 activity at 10−3 M, a property not shared by manoyl oxide F1. We conclude that these two natural products interact with the eicosanoid system, perhaps at the phospholipase level, but do not interfere with the other tested leukocyte functions or with reactive oxygen species, and are essentially non-toxic at the doses used.
    Type of Medium: Electronic Resource
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