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SHR Neuro Cancer Cardio Lipid Metab Microb

Traeger, T; Kessler, W; Assfalg, V; Cziupka, K; Koerner, P; Dassow, C; Breitbach, K; Mikulcak, M; Steinmetz, I; Pfeffer, K; Heidecke, CD; Maier, S.
Detrimental role of CC chemokine receptor 4 in murine polymicrobial sepsis.
Infect Immun. 2008; 76(11):5285-5293 Doi: 10.1128/IAI.00310-08 [OPEN ACCESS]
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Co-authors Med Uni Graz: Steinmetz Ivo
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Abstract:: CC chemokine receptor 4 (CCR4) and its two ligands, CCL17 and CCL22, are critically involved in different immune processes. In models of lipopolysaccharide-induced shock, CCR4-deficient (CCR4(-/-)) mice showed improved survival rates associated with attenuated proinflammatory cytokine release. Using CCR4(-/-) mice with a C57BL/6 background, this study describes for the first time the role of CCR4 in a murine model of polymicrobial abdominal sepsis, the colon ascendens stent peritonitis (CASP). CASP-induced sepsis led to a massive downregulation of CCR4 in lymphoid and nonlymphoid tissues, whereas the expression of CCL17 and CCL22 was independent of the presence of CCR4. After CASP, CCR4(-/-) animals showed a strongly enhanced bacterial clearance in several organs but not in the peritoneal lavage fluid and the blood. In addition, significantly reduced levels of proinflammatory cytokines/chemokines were measured in organ supernatants as well as in the sera of CCR4(-/-) mice. CCR4 deficiency consequently resulted in an attenuated severity of systemic sepsis and a strongly improved survival rate after CASP or CASP with intervention. Thus, our data provide clear evidence that CCR4 plays a strictly detrimental role in the course of polymicrobial sepsis.
Find related publications in this database (using NLM MeSH Indexing): Animals -; Apoptosis - immunology; Chemokine CCL17 - immunology; Chemokine CCL17 - metabolism; Chemokine CCL22 - immunology; Chemokine CCL22 - metabolism; Chemokines - immunology; Female -; Macrophages - immunology; Mice -; Mice, Inbred C57BL -; Peritonitis - immunology; Peritonitis - metabolism; Receptors, CCR4 - immunology; Receptors, CCR4 - metabolism; Reverse Transcriptase Polymerase Chain Reaction -; Sepsis - immunology