Defense Date

1992

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Microbiology & Immunology

First Advisor

Thomas F. Huff

Abstract

Stem cell factor (SCF) is a recently characterized hematopoietic growth factor capable of stimulating the proliferation and differentiation of many hematopoietic cells, including the mast cell. We have cloned the gene encoding SCF from a cDNA library prepared from NIH 3T3 fibroblasts, and have characterized the ability of recombinant SCF to induce the development of mast cell-committed progenitors (MCCP), found in the mesenteric lymph nodes of mice infected with Nippostrongylus brasiliensis (Nb-MLN), but not naive mice. We have also examined Schwann cells, mast cells, and reproductive tissues for their ability to produce SCF.

We have found that recombinant SCF alone can promote the formation of mast cell colonies from MCCP in methylcellulose. SCF affected not only MCCP proliferation, but could also induce their differentiation to connective tissue phenotype mast cells. SCF was also capable of generating mast cell colonies from precursors found in the peritoneal cavity of naive mice. Unexpectedly, infection of mice with Nippostrongylus caused a loss of the precursors from the peritoneal cavity by 14 days after infection.

Mast cells are found near Schwann cells, and increases in mast cells have been noted concomitant with Schwann cell neoplasia, and nerve damage and repair. Schwann cells from several sources were shown to produce mRNA for SCF, and the protein was also detected on the cell surface by immunofluorescent staining, or as a secretable product in cell-conditioned supernatant. Schwann cells were also analyzed for the ability to produce the receptor for SCF, c-kit. Immunofluorescent staining and polymerase chain reaction (PCR) analysis has shown that a human malignant schwannoma expresses c-kit, while normal human Schwann cells as well as SV-40 transfected, primary neonatal and primary adult rat Schwann cells do not. Thus normal production of SCF could form an autocrine growth loop in some Schwann cell neoplasias which aberrantly express c-kit.

Lastly, rat and human reproductive tissues were examined for expression of the SCF gene, using PCR and northern analysis. We found that SCF is expressed in a differential manner by various maternal and fetal tissues during pregnancy and the menstrual cycle. While rat tissues contained easily detectable SCF mRNA, human tissues appeared to express this gene in a lower quantity.

Comments

Scanned, with permission from the author, from the original print version, which resides in University Archives.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

4-6-2018

Included in

Microbiology Commons

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