| Autor: |
Contaldo, Claudio, Lindenblatt, Nicole, Elsherbiny, Ahmed, Högger, Dominik C., Borozadi, Meisam Khorrami, Vetter, Sebastian T., Lang, Karl S., Handschin, Alexander E., Giovanoli, Pietro |
| Zdroj: |
Shock; March 2011, Vol. 35 Issue: 3 p315-321, 7p |
| Abstrakt: |
In the present study, we aimed to evaluate whether erythropoietin (EPO) treatment may exert nonhematopoietic endothelial protection against TNF--induced microvascular inflammation and to determine the involvement of the nitric oxide (NO)-producing enzyme isoforms endothelial NO synthase (eNOS) and inducible NO synthase (iNOS). Murine dorsal skinfold chambers of wild-type (WT) animals were topically stimulated with TNF- after pretreatment with epoetin beta (1,000 IU/kg body weight i.p.) or physiological saline. Leukocyte behavior, microvascular perfusion, and apoptosis were assessed by in vivofluorescence microscopy. To study the involvement of NO, we compared eNOS-deficient (eNOS−/−) and iNOS-deficient (iNOS−/−) mice with WT animals. TNF--associated leukocyte activation, perfusion failure, and apoptosis were substantially attenuated in EPO-pretreated WT mice, which was accompanied by marked reduction of perivascular infiltration with F4/80-stained macrophages. The anti-inflammatory protective effects of EPO were abolished in eNOS−/−, but not in iNOS−/−mice, both with unaffected intercellular adhesion molecule 1 expression. However, the antiapoptotic effect of EPO was maintained in both eNOS−/−and iNOS−/−mice, indicating that this mechanism might rather be independent of NO. We conclude that EPO treatment elicits protection against TNF--induced microcirculatory dysfunction, depending on NO derived from endothelial cells, but not on the inducible isoform. |
| Databáze: |
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