An Extract of the Tapeworm, Hymenolepis diminuta, Inhibits Neutrophil Migration in vitro

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atmire.migration.oldid6173
dc.contributor.advisorMcKay, Derek
dc.contributor.advisorGilleard, John
dc.contributor.authorGraves, Nicholas
dc.contributor.committeememberYipp, Bryan
dc.contributor.committeememberFinney, Constance
dc.date.accessioned2017-11-08T15:56:26Z
dc.date.available2017-11-08T15:56:26Z
dc.date.issued2017
dc.date.submitted2017en
dc.description.abstractNeutrophils are not typically the first cell that comes to mind when the immune response to infection with helminths is considered. However, data are emerging showing that these cells may play an overlooked role in response to helminths perhaps early in the infection and particularly those species that cause tissue damage (e.g. Nippostrongylus brasiliensis - a gut nematode (roundworm)). Additionally, different helminth products have been shown to directly activate neutrophils in vitro (e.g. crude extracts of the porcine cestode Cysticercus cellulosae) and directly induce their chemotaxis (e.g. excretory/secretory products of the sheep nematode Haemonchus contortus). Hymenolepis diminuta crude extract (HdE) has been shown to inhibit dinitrobenzene sulfonic acid-induced colitis. Intraperitoneal injection of this crude extract recruited a population of peritoneal exudate cells dominated by neutrophils at 4h post-injection. Remarkably, these neutrophil-predominant PECs evoked increased production of the anti-inflammatory cytokine IL-10 from co-cultures of activated murine splenic CD4+ T cells. HdE did not directly induce murine neutrophil chemotaxis in vitro and direct application of HdE to neutrophils was not preferentially cytotoxic as assessed by trypan blue staining and LDH release. HdE did however induce Ca2+ mobilization and respiratory burst by murine neutrophils in vitro. In contrast to its ability to recruit neutrophils to the peritoneal cavity, HdE inhibited neutrophil chemotaxis in response to WKYMVm and keratinocyte derived chemokine (KC). HdE was unable to modulate neutrophil migration towards leukotriene B4. Biochemical characterizations (boiling, trypsinization, acidification, and sodium metaperiodate treatment) suggested that an acid-stable glycoprotein was responsible for its ability to block migration towards WKYMVm. The ability of HdE to block migration towards WKYMVm appears to be independent of the phosphorylation of the mitogen-activated protein kinase, p38. HdE did not directly induce production of the cytokines, IL-10, TNF-α, and KC. It also did not modulate production of these cytokines induced by other activators. In conclusion: (1) HdE activated neutrophils to mobilize Ca2+ into the cytoplasm and produce ROS; and, (2) an acid-stable glycoprotein component of the HdE inhibited neutrophil migration towards WKYMVm.en_US
dc.identifier.citationGraves, N. (2017). An Extract of the Tapeworm, Hymenolepis diminuta, Inhibits Neutrophil Migration in vitro (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/24897en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/24897
dc.identifier.urihttp://hdl.handle.net/11023/4240
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectImmunology
dc.subject.otherneutrophils
dc.subject.otherhelminth
dc.subject.otherparasite
dc.subject.otherreactive oxygen species
dc.titleAn Extract of the Tapeworm, Hymenolepis diminuta, Inhibits Neutrophil Migration in vitro
dc.typemaster thesis
thesis.degree.disciplineGastrointestinal Sciences
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
ucalgary.item.requestcopytrue
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