Date of Award

Fall 12-1-2003

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Life Sciences

First Advisor

Swapan K. Ghosh

Second Advisor

Mary T. Johnson

Third Advisor

J. Chen

Abstract

Multiples myelomas are untreatable neoplasias in humans, arising from terminally differentiated B cells (plasma cells). The murine pristane-induced plasmacytoma model offers a system for studying the cellular interactions involved in sustaining the growth of plasma cell tumors. In accord with this model, syngenic plasma cell tumors transplanted into the peritoneal cavity of a genetically susceptible mouse are normally cleared by the mouse's immune system. If the mouse is pretreated with pristane (2,6,10,14- tetramethylpentadecane) intraperitoneally, prior to the transplantation of the plasma cell tumor, the tumor thrives, culminating in the death of the mouse. Intraperitoneal administration of pristane results in an influx of macrophages, T cells and neutrophils. The purpose of this study was to determine the role of the macrophages in supporting tumor growth. To address this question, the phenotype of peritoneal macrophages recruited to the peritoneal cavity of IDH PEP3 mice was analyzed by flow cytometry. Based on surface expression ofMac-1, F4/80 and Gr-1, myeloid suppressor cells were identified in the peritoneal cavity, capable of suppressing the proliferation of splenocytes in a contact dependent manner. Phenotypically similar cells were not found in the peritoneal cavity of DBA/2n mice following pristane priming. In a separate study, the nitric oxide lV synthase and arginase activities were evaluated in peritoneal macrophages. Active nitric oxide synthase is indicative of the production of anti-tumor compounds (nitric oxide) while active arginase is indicative of the production of pro-tumor compounds (polyamines). Peritoneal monocytes from non-pristanized mice had low arginase activity and high nitric oxide activity following tumor challenge. In contrast, peritoneal monocytes from pristane-primed mice had high arginase activity and low inducible nitric oxide synthase activity following tumor challenge. Collectively, these data suggest that monocytes in the peritoneal environment may promote rather than reduce tumor growth through immune suppression and the production of tumor promoting compounds.

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