Article: Tilmicosin-induced bovine neutrophil apoptosis is cell-specific and downregulates spontaneous LTB4 synthesis without increasing Fas expression.
2004 Volume 35, Issue 2, Page(s) 213–224
Abstract: The pathology of bacterial pneumonia, such as seen in the bovine lung infected with Mannheimia haemolytica, is due to pathogen virulence factors and to inflammation initiated by the host. Tilmicosin is a macrolide effective in treating bacterial ... ...
| Abstract | The pathology of bacterial pneumonia, such as seen in the bovine lung infected with Mannheimia haemolytica, is due to pathogen virulence factors and to inflammation initiated by the host. Tilmicosin is a macrolide effective in treating bacterial pneumonia and recent findings suggest that this antibiotic may provide anti-inflammatory benefits by inducing polymorphonuclear neutrophilic leukocyte (PMN) apoptosis. Using an in vitro bovine system, we examined the cell-specificity of tilmicosin, characterized the changes in spontaneous leukotriene B4 (LTB4) synthesis by PMN exposed to the macrolide, and assessed its effects on PMN Fas expression. Previous findings demonstrated that tilmicosin is able to induce PMN apoptosis. These results were confirmed in this study by the Annexin-V staining of externalized phosphatidylserine and the analysis with flow cytometry. The cell-specificity of tilmicosin was assessed by quantification of apoptosis in bovine PMN, mononuclear leukocytes, monocyte-derived macrophages, endothelial cells, epithelial cells, and fibroblasts cultured with the macrolide. The effect of tilmicosin on spontaneous LTB4 production by PMN was evaluated via an enzyme-linked immunosorbent assay. Finally, the mechanisms of tilmicosin-induced PMN apoptosis were examined by assessing the effects of tilmicosin on surface Fas expression on PMN. Tilmicosin-induced apoptosis was found to be at least partially cell-specific, as PMN were the only cell type tested to die via apoptosis in response to incubation with tilmicosin. PMN incubated with tilmicosin under conditions that induce apoptosis spontaneously produced less LTB4, but did not exhibit altered Fas expression. In conclusion, tilmicosin-induced apoptosis is specific to PMN, inhibits spontaneous LTB4 production, and occurs through a pathway independent of Fas upregulation. |
|---|---|
| MeSH term(s) | Animals ; Apoptosis/drug effects ; Cattle ; Flow Cytometry/veterinary ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/metabolism ; Leukotriene B4/biosynthesis ; Macrolides/pharmacology ; Macrolides/therapeutic use ; Macrophages/drug effects ; Macrophages/metabolism ; Mannheimia haemolytica/drug effects ; Pasteurellosis, Pneumonic/drug therapy ; Pasteurellosis, Pneumonic/microbiology ; Phagocytosis/drug effects ; Tylosin/analogs & derivatives ; Tylosin/pharmacology ; Tylosin/therapeutic use |
| Chemical Substances | Macrolides ; Leukotriene B4 (1HGW4DR56D) ; tilmicosin (XL4103X2E3) ; Tylosin (YEF4JXN031) |
| Language | English |
| Publishing date | 2004-03 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 1146298-x |
| ISSN | 1297-9716 ; 0928-4249 |
| ISSN (online) | 1297-9716 |
| ISSN | 0928-4249 |
| DOI | 10.1051/vetres:2004004 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.B 1313: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.