Role of interleukin-8 monomer-dimer equilibrium and glycosaminoglycan interactions in neutrophil recruitment

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dc.contributor.advisorDr. Sarita Sastryen_US
dc.contributor.committeeMemberDr. Roberto Garofaloen_US
dc.contributor.committeeMemberDr. Krishna Rajarathnamen_US
dc.creatorPavani Kumari Gangavarapuen_US
dc.date.accessioned2011-12-20T16:05:13Z
dc.date.available2008-12-09en_US
dc.date.available2011-12-20T16:05:13Z
dc.date.created2008-08-25en_US
dc.date.issued2008-08-08en_US
dc.description.abstractChemokines are small, soluble secreted proteins that induce cell migration through activation of G Protein Coupled Receptors (GPCR), and also bind extracellular matrix\r\nglycosaminoglycans (GAG) for recruiting target cells. Interleukin-8 (IL-8) is a proinflammatory chemokine, recruits neutrophils as a host response to infection and tissue injury.. An imbalance in the recruitment process has been attributed to a variety of autoimmune and inflammatory diseases. Knowledge of in vivo IL-8„ŸGAG interactions is one of the first steps towards understanding the in vivo physiology and molecular mechanisms regulating neutrophil recruitment. All chemokines including IL-8 exist as both monomers and dimers and in vitro studies have shown that both monomers and dimers of IL-8 can bind to GPCRs and GAGs, though with different affinities and specificities. However, the role of monomers, and dimers and of monomer-dimer equilibrium in regulating in vivo IL-8 function is not known. We hypothesize that the dynamic equilibrium between monomers and dimers in solution and in GAG-bound form is essential for regulation of in vivo neutrophil recruitment. Studying the role of monomers and dimers in isolation is experimentally challenging, as the monomers and dimers exist in equilibrium. This equilibrium prevents studying one species without interference from the other. We used an innovative approach, where we have used obligate monomers and obligate dimers to overcome this hurdle, and have studied the role of monomer-dimer equilibrium and GAG-binding in neutrophil recruitment. The knowledge from this study could provide valuable information for the inhibition of chemokine function, and be used for designing drugs for inflammatory and autoimmune diseases.\r\nen_US
dc.format.mediumelectronicen_US
dc.identifier.otheretd-08252008-100443en_US
dc.identifier.urihttp://hdl.handle.net/2152.3/216
dc.language.isoengen_US
dc.rightsCopyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works.en_US
dc.subjectInterleukin-8en_US
dc.subjectglycosaminoglycanen_US
dc.subjectchemokinesen_US
dc.titleRole of interleukin-8 monomer-dimer equilibrium and glycosaminoglycan interactions in neutrophil recruitmenten_US
dc.type.genrethesisen_US
dc.type.materialtexten_US
thesis.degree.departmentBiochemistry and Molecular Biologyen_US
thesis.degree.grantorThe University of Texas Medical Branchen_US
thesis.degree.levelMasteren_US
thesis.degree.nameMaster of Scienceen_US

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