Accession Number:

ADA634932

Title:

Heterogeneity Within Macrophage Populations: A Possible Role for Colony Stimulating Factors

Descriptive Note:

Doctoral thesis

Corporate Author:

UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD

Personal Author(s):

Report Date:

1988-04-04

Pagination or Media Count:

218.0

Abstract:

These studies were undertaken in an attempt to elucidate the raison detre for the existence of two distinct Colony Stimulating Factors CSFs whose site of action is believed to be the same bone marrow progenitor and whose differentiated mononuclear end cell is presumed to be identical. Through a side by side comparison, we have explored this question of apparent cytokine redundancy by examining the responsiveness of murine bone marrow progenitors to highly purified or recombinant preparations of GM-CSF and CSF-1, in both soft agar and liquid cultures. Our findings show that the number of CSF-1-responsive progenitor cells which formed colonies in soft agar was approximately six-fold greater than the number of progenitors which responded to GM-CSF. However, upon stimulation of bone marrow progenitors in soft agar culture with both GM-CSF and CSF-1, we observed the development of a significant percentage of very large colonies 2 mm in diameter. These progenitors were present in the bone marrow of both untreated mice and in mice which had been administered the cytotoxic drug, 5-fluorouracil, consistent with descriptions of a primitive progenitor population which exhibits high proliferative potential HPP-CFC . In addition, the macrophages which developed under the influence of either GM-CSF or CSF-1 in liquid culture were found to differ morphologically and functionally. Although CSF-1 -derived macrophages were shown to be superior in their phagocytic capacities and the ability to resist viral infection, GM-CSF-derived macrophages exhibited very high Ia antigen expression, an augmented ability to induce antigen-specific T cell proliferation, and a greater potential for tumoricidal activity. These findings suggest that the acquisition of higher order macrophage functions i.e., typically associated with highly activated macrophages may not require a differentiative progression which results in the retention of certain lower order functions. Our findings al

Subject Categories:

  • Biochemistry
  • Biology
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE