Show simple item record

dc.contributor.advisor Stern, Michael
dc.creatorMaharjan, Anu
dc.date.accessioned 2012-09-05T23:50:50Z
dc.date.accessioned 2012-09-05T23:51:07Z
dc.date.available 2012-09-05T23:50:50Z
dc.date.available 2012-09-05T23:51:07Z
dc.date.created 2012-05
dc.date.issued 2012-09-05
dc.date.submitted May 2012
dc.identifier.citation Maharjan, Anu. "Regulation of Innate Immune Cells." (2012) Diss., Rice University. https://hdl.handle.net/1911/64607.
dc.identifier.urihttps://hdl.handle.net/1911/64607
dc.description.abstract Immune cells such as neutrophils and monocytes enter tissues after tissue damage and clear cell debris to allow repair cells such as fibroblasts to close the wound. Monocytes also differentiate into fibroblast-like cells called fibrocytes to mediate wound healing, similar to fibroblasts. However, in abnormal wound healing such as acute respiratory distress syndrome (ARDS) and fibrosing diseases, the accumulation of immune cells such as neutrophils or fibrocytes become detrimental to health. In ARDS, neutrophils accumulate in the lungs and causes additional damage by producing reactive oxygen species (ROS). In fibrosing diseases, increased fibrocyte differentiation is one of the causes that increase extracellular matrix deposition, which leads to severe scar tissue build up. Since there are no effective treatments for ARDS or fibrosing diseases, understanding the regulation of neutrophil activation or fibrocyte differentiation could be helpful to develop new effective therapies. The Gomer lab has found several factors that either promote or inhibit fibrocyte differentiation. The pro-fibrotic cytokines such as IL-4 and IL-13 potentiate fibrocyte differentiation while the plasma protein serum amyloid P (SAP), crosslinked IgG, and the pro-inflammatory cytokines IFN-γ and IL-12 inhibit fibrocyte differentiation. In this thesis, I have now shown that additional factors such as toll-like receptor 2 (TLR2) agonists and low molecular weight hyaluronic acid (LMWHA) inhibit fibrocyte differentiation, while high molecular weight hyaluronic acid (HMWHA) potentiate fibrocyte differentiation. The accumulation of neutrophils in the lungs is one of the major factors that debilitate the health of a patient in ARDS. Since neutrophils have Fc receptors, I examined the effect of SAP on neutrophil spreading, adherence, activation, and accumulation. SAP inhibits neutrophil spreading induced by cell debris and TNF-α induced adhesion, but SAP is unable to have any effect on classic neutrophil adhesion molecules or the production of hydrogen peroxide. SAP inhibits neutrophil accumulation in the lungs of bleomycin-injured mice. There is an exciting possibility of using SAP as a therapeutic agent to treat ARDS.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.subjectFibrocyte
Monocyte
Fibrosis
Hyaluronic acid
Neutrophil
Acute respiratory distress syndrome (ARDS)
Acute lung injury
Adhesion
dc.title Regulation of Innate Immune Cells
dc.type Thesis
dc.contributor.committeeMember Bennett, George N.
dc.contributor.committeeMember Braam, Janet
dc.contributor.committeeMember Grande-Allen, K. Jane
dc.date.updated 2012-09-05T23:51:07Z
dc.identifier.slug 123456789/ETD-2012-05-45
dc.type.material Text
thesis.degree.department Biochemistry and Cell Biology
thesis.degree.discipline Natural Sciences
thesis.degree.grantor Rice University
thesis.degree.level Doctoral
thesis.degree.name Doctor of Philosophy


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record