Project: Research project

Project Details


Inflammation is a complex host response that involves several biochemical
pathways and all hemopoietic elements. T lymphocytes play an integral role
in inflammatory responses by secreting soluble protein factors,
lymphokines, that can regulate both the immunospecific and generalized
aspects of the response. The first cells to arrive at a site of
inflammation are neutrophilic granulocytes; macrophages usually appear
several hours after granulocytes. Cloned T lymphocytes are a potent source
of factors that affect hemopoiesis. The major hemopoietically active
factor that is secreted by T lymphocytes is a granulocyte-macrophage
colony-stimulating factor (GM-CSF). During an inflammatory response this
GM-CSF may act distally on bone marrow cells to increase the number of
responding granulocytes and macrophages. A major goal of this project is
to purify to homogeneity the T lymphocyte GM-CSF. A highly enriched
preparation of GM-CSF has been obtained with the use of high-pressure
liquid chromatography. When serum free T lymphocyte-conditioned medium is
used as a starting material, the GM-CSF will be purified to homogeneity.
Another aim of this project is to determine the nature of the interaction
between GM-CSF, IL3 (which is also produced by T lymphocytes), and
erythropoietin. It has been shown already tha IL3 potentiates the effects
of erythropoietin. However, T lymphocytes secrete about 10-100-fold more
GM-CSF than IL3; the molecular basis for the net effect on bone marrow
cells when all three factors are present in physiological or
pathophysiological (i.e. during inflammation) concentrations is unknown but
testable with pure factors. In addition, homogeneous GM-CSF will be
subjected to mild proteolysis in an attempt to produce biologically active
peptides to determine the minimal structural requirements that are
necessary for biological activity. A longterm goal of this project will be
to synthesize chemically bioactive peptides and structural analogs that can
be used as either stimulatory or inhibitory effectors of hemopoiesis.
These studies will further our understanding of the role that T lymphocytes
play in regulating hemopoiesis.
Effective start/end date12/31/891/1/90


  • Filtration and Separation


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