Horses are prone to potentially lethal endotoxemia due to their surrounding fecal containing environment and their predisposition to colic. Their gastrointestinal tract and feces naturally contain gram-negative bacteria. These bacteria express lipopolysaccharide (LPS) on their cell membranes, which is recognized by Toll-like receptor 4 (TLR4). In cases where epithelial barriers are compromised or breached LPS has the potential to enter circulation and cause the inflammatory symptoms seen with endotoxemia. The objective of this study was to determine TLR4 presence and functionality on equine B cells. TLR4 expression on B lymphocytes has been studied in mouse, human and many other mammals, but has not been well characterized in the horse. Humans are highly sensitive to LPS but their B cells express non-functional TLR4. Mice in contrast are highly tolerant of LPS yet their B cells express functional TLR4. Studies in horse have perhaps been limited by the limited array of antibody markers available for use in horse. Anti-human CD21 has previously been shown to mark equine B lymphocytes. We show rat anti-mouse CD45R(B220) mAbs also accurately labels equine B lymphocytes. To investigate TLR4 expression in horses 12 Thoroughbred geldings, ages 5-10, were used for blood collection. By using the density gradient, Lympholyte, lymphocytes were separated from peripheral blood and incubated with or without LPS. B lymphocyte proliferation, TLR4 expression and mRNA changes were examined before or after culture in the presence or absence of LPS. We demonstrate TLR4 is expressed on equine B lymphocytes through the use of a mouse anti-human TLR4 antibody, clone 76B357.1, not previously used in horse. We demonstrated equine B cells fail to proliferate under LPS challenge as opposed to highly proliferative mouse B lymphocytes. However, transcriptional changes were observed in the equine cells within the TLR4 pathway upon treatment with LPS. / Master of Science / Horses are prone to potentially lethal infections due to their surrounding fecal containing environment and their predisposition to colic. Their gastrointestinal tract and environment naturally contain gram-negative bacteria such as E.coli. The gram-negative bacterial cell membrane expresses a molecule called lipopolysaccharide (LPS) which can cause inflammation by binding to an immune cell receptor called toll-like receptor 4 (TLR4). In cases where epithelial barriers are compromised or breached, LPS has the potential to enter the circulation and cause a severe inflammatory response capable of progressing to shock and death. Humans are also highly sensitive to LPS yet their B lymphocytes express non-functional TLR4. Mice, in contrast, are highly tolerant of LPS but their B lymphocytes express functional TLR4. The objective of this study was to determine TLR4 presence and functionality on equine B lymphocytes. Studies in horse have perhaps been limited by the small number of antibody markers available for use in horse. Two B lymphocyte markers not previously assessed in horse tissue were used in this experiment to enrich for B lymphocytes. A TLR4 marker, also not previously described in the horse, was used in conjunction with the two B lymphocyte markers determined TLR4 is present on equine B lymphocytes. However, equine B lymphocytes failed to proliferate in the presence of LPS similiar to human B cells. Transcriptional changes were observed in the equine cells in the TLR4 pathway upon treatment with LPS.

Thesis (doctoral)--Lund University, 1998. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 1998. / Vita. Includes bibliographical references (leaves [83]-98).

Thesis (doctoral)--Københavns universitet.

Thesis (doctoral)--Groningen, 1981.

Thesis (Ph.D.) -- Virginia Commonwealth University, 2006. / Prepared for: Dept. of Microbiology and Immunology. Bibliography: p. 152-184. Also available online.

In the world today, asthma affects more than 235 million people. The widespread prescription of inhaled corticosteroids—the current gold standard of asthma control medication—allows many asthmatics to live symptom-free and has significantly reduced the number of deaths due to asthma. However, when the disease is poorly controlled, for example due to ubiquitous exposure to airborne fungal conidia, this chronic inflammatory disease often results in lung dysfunction caused by airway architectural changes. The role of B lymphocytes in allergic asthma has been relegated to the production of IgE with relatively little being known about the trafficking of these cells in the tissues or their role(s) in the affected tissue. As a first step in ascertaining their function, the initial aim of this project was to characterize the recruitment and localization of B cells in the murine lung in response to Aspergillus fumigatus inhalation. We found that CD19+CD23+ B2 lymphocytes were recruited to the lungs after fungal inhalation and that IgA-, IgE-, IgG-producing cells localized around the large airways. The second aim of the project was to begin defining the impact that these B lymphocytes have on the allergic lung. By using mice that were deficient of conventional B cells, we were able to demonstrate that the allergic phenotype was retained, although the impact of tissue B1 B cells cannot yet be ruled out. We then investigated the ability of hyaluronic acid (HA), a major component of the extracellular matrix (ECM) generated at sites of chronic inflammation, to recruit and modulate B lymphocyte functions in allergic fungal disease. We found that B lymphocytes undergo chemotaxis in response to LMM HA, while HMM HA had little to no effect on B cell chemotaxis. Furthermore, HA-mediated B lymphocyte chemotaxis was significantly inhibited by blocking the CD44 HA receptor. We also demonstrated that LMM HA fragments elicit the production of the pro-fibrotic cytokines IL-10 and TGF-β1 by B lymphocytes. These observations suggest a previously unrecognized role for B lymphocytes and HA in the context of allergy and represent novel pathways by which B lymphocytes may contribute to airway inflammation and airway remodeling.

Thesis (Ph. D.)--University of Missouri--Columbia, 2000. / "December 2000." Typescript. Vita. Includes bibliographical references (leaves 177-206). Also available on the Internet.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.