ALBERT

Description: Elevated leukotriene (LT)C4 synthase activity was observed in peripheral blood granulocyte suspensions from patients with chronic myeloid leukemia (CML). Magnetic cell sorting (MACS) with CD16 monoclonal antibodies (mAbs), which were used to fractionate granulocytes from CML patients and healthy individuals, yielded highly purified suspensions of CD16+ neutrophils. The purity of these cell fractions was verified by extensive morphologic examination. Reverse transcriptase–polymerase chain reaction (RT-PCR) analyses, demonstrating the absence of interleukin-4 messenger RNA (IL-4 mRNA), further confirmed the negligible contamination of eosinophils in these fractions. Notably, purified CML CD16+ neutrophils from all tested patients transformed exogenous LTA4 to LTC4. These cells also produced LTC4 after activation with ionophore A23187 or the chemotactic peptide fMet-LeuPhe (N-formylmethionyl-leucyl-phenylalanine). Subcellular fractionation revealed that the enzyme activity was exclusively distributed to the microsomal fraction. Expression of LTC4 synthase mRNA in CML CD16+neutrophils was confirmed by RT-PCR. Furthermore, Western blot analyses consistently demonstrated expression of LTC4 synthase at the protein level in CML CD16+ neutrophils, whereas expression of microsomal glutathione S-transferase 2 occurred occasionally. Expectedly, LTC4 synthase activity or expression of the protein could not be demonstrated in CD16+ neutrophil suspensions from any of the healthy individuals. Instead, these cells, as well as CML CD16+neutrophils, transformed LTA4 to LTB4. The results indicate that aberrant expression of LTC4 synthase is a regular feature of morphologically mature CML CD16+neutrophils. This abnormality, possibly associated with malignant transformation, can lead to increased LTC4 synthesis in vivo. Such overproduction may be of pathophysiological relevance because LTC4 has been demonstrated to stimulate proliferation of human bone marrow–derived myeloid progenitor cells.

Description: A transient model simulation from 1960 to 2000 with the coupled climate-chemistry model (CCM) shows a stratospheric water vapor trend during the last two decades of +0.7 ppmv and additionally a short-term increase during volcanic eruptions. At the same time this model simulation shows a long-term decrease in total ozone and a short-term tropical ozone decline after a volcanic eruption. In order to understand the resulting effects of the water vapor changes on stratospheric ozone chemistry, different perturbation simulations have been performed with the CCM with the water vapor perturbations fed only to the chemistry part. Two different long-term perturbations of stratospheric water vapor, +1 ppmv and +5 ppmv, and a short-term perturbation of +2 ppmv with an e-folding time of two months have been simulated. Since water vapor acts as an in-situ source of odd hydrogen in the stratosphere, the water vapor perturbations affect the gas-phase chemistry of hydrogen oxides. An additional water vapor amount of +1 ppmv results in a 5–10%  increase. Coupling processes between and / also affect the ozone destruction by other catalytic reaction cycles. The  cycle becomes 6.4% more effective, whereas the cycle is 1.6% less effective. A long-term water vapor increase does not only affect the gas-phase chemistry, but also the heterogeneous ozone chemistry in polar regions. The additional water vapor intensifies the strong denitrification of the Antarctic winter stratosphere caused by an enhanced formation of polar stratospheric clouds. Thus it further facilitates the catalytic ozone removal by the cycle. The reduction of total column ozone during Antarctic spring peaks at −3%. In contrast, heterogeneous chemistry during Arctic winter is not affected by the water vapor increase. The short-term perturbation studies show similar patterns, but because of the short perturbation time, the chemical effect on ozone is almost negligible. Finally, this study shows that 10% of the simulated long-term ozone decline in the transient model simulation can be explained by the water vapor increase, but the simulated tropical ozone decrease after volcanic eruptions is caused dynamically rather than chemically.