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Title: Role of serosal cavity resident leukocytes in the orchestration of leukocyte recruitment following the induction of experimental inflammation
Author: Cailhier, Jean-Francois Henry
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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This study evaluate the role of resident peritoneal and pleural macrophages (Mф) in neutrophil (PMN) recruitment in acute peritoneal and pleural inflammation. I also investigated the role of Lp in peritoneal inflammation by studying experimental peritonitis in mice deficient in various lymphocyte populations. The conditional Mф ablation mice used in these studies are transgenic for the human diphtheria toxin receptor (DTR) under the CD11b promoter (CD11b-DTR mice) and exhibit >97% depletion of resident serosal Mф following intraperitoneal (IP) administration of diphtheria toxin (DT). Mф ablation markedly inhibited peritoneal and pleural PMN recruitment at early time points compared to wild type (WT) controls. Administration of Mф-rich resident cells, unlike Mф-depleted resident cells, significantly restored PMN infiltration. Analysis of PMN C-X-C chemokines in lavage exudates showed that Mф-depleted mice had significantly reduced levels of peritoneal and pleural MIP-2 and KC at the 1hr time point compared to control mice and more marked MIP-2 reduction compared to KC (>90% reduction vs 25-40%). Reduced levels of monocyte C-C chemokine and various cytokines were evident in the Mф-depleted mice at early time points. In vitro studies demonstrated that the production of these chemokines and cytokines from peritoneal and pleural cells was Mф-dependent. RAG-1 KO mice exhibited increased early PMN infiltration and blunted Mф infiltration. NUDE exhibited increased early PMN infiltration and increased Mф infiltration whilst μMT KO mice exhibited decreased PMN influx and a reduced Mф influx. Although chemokine analysis of peritoneal exudates in RAG-1 KO mice and NUDE mice demonstrated some differences in MCP-1 levels, there were no clear differences evident in μMT KO mice.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available