Challenge of the immune system with bacterial superantigens or endotoxin induces the systemic release of cytokines followed by lethal septic shock. The lung is particularly susceptible to systemic toxin exposure resulting in acute leucocyte infiltration and vascular damage. In the present study, the functions of interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) for chemokine regulation during acute lung inflammation were examined. Following administration of the superantigen, staphylococcal enterotoxin B (SEB), lung mRNA levels of the chemokines cytokine-induced neutrophil chemo-attractant (KC), lipopolysaccharide-induced CXC chemokine (LIX), macrophage chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1alpha and MIP-2 were increased to a similar extent both in controls and in mice deficient for the IFN-gamma or 55 000 MW TNF receptors. In contrast, interferon-inducible protein-10 (IP-10) and monokine induced by IFN-gamma (Mig) mRNA expression was markedly reduced in mice deficient for IFN-gamma or IFN-gamma receptor, but not in 55 000 MW TNF receptor knockout mice. In situ hybridization experiments demonstrated that IP-10 was highly expressed in lung interstitial macrophages of C57BL/6, but not of IFN-gamma receptor-deficient mice. In contrast to SEB administration, treatment with lipopolysaccharide resulted in a strong induction of IP-10 and Mig in IFN-gamma receptor-deficient mice. Together, these results establish a critical function of IFN-gamma for chemokine induction in acute lung inflammation that is dependent on the nature of the inflammatory stimulus.
Willebrand factor ristocetin cofactor activity assay using a novel automated assay protocol. J Thromb Haemost 2010; 8: 2216-23.Summary. Background, objectives and methods: An accurate, sensitive and precise assay for reliable determination of the ristocetin cofactor activity of von Willebrand factor (VWF:RCo) in plasma and von Willebrand Factor (VWF)-containing concentrates has been evaluated. The assay is based on a commercially available automated protocol with modifications including a combination of adding additional ristocetin and the use of two calibration curves for the high and low measuring ranges. Results: Addition of extra ristocetin resulted in improved measurement of VWF recoveries from various VWF-containing concentrates that were underestimated using the standard automated protocol. The modifications resulted in improved assay performance over an extended measuring range (2.00-0.03 IU mL )1). Accuracy was tested using VWF deficiency plasma spiked with the 1st international standard (IS) for VWF concentrate. Seven dilutions, ranging from 1.80 to 0.05 IU mL )1, were analyzed and resulted in measured concentrations between 80% and 100% of the assigned potency of the standard. Linearity was determined from the regression plot of the same concentrate dilutions and resulted in a correlation coefficient of 0.998. The repeatability, expressed as coefficient of variation, was 2% in the normal range (0.90 IU mL . The corresponding reproducibility results were 2% and 15% at the normal and low measuring ranges, respectively. Conclusions: Analysis of patients with von Willebrand disease (VWD) indicates that the modified automated BCS Ò protocol has a superior discrimination power compared with the standard protocol. This is especially true in samples with low VWF, as in patients with type 3 VWD.
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