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) : Falk, Lydia A


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a634932.pdf


Report Date : 04 Apr 1988


Pagination or Media Count : 218


Abstract : These studies were undertaken in an attempt to elucidate the raison d'etre 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


Descriptors :   *BONE MARROW , *COLONIES(BIOLOGY) , *HETEROGENEITY , *MACROPHAGES , AGAR , ANTIGENS , ASSAYING , CELLS(BIOLOGY) , T LYMPHOCYTES


Subject Categories : Biochemistry
      Biology
      Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE