Differentiation and activation of functionally distinct macrophage populations by CSF-1 and GM-CSF

Macrophages derived in vitro from bone marrow progenitor cells (BMDM) under the influence of CSF-1 or GM-CSF were compared for immune function. CSF-1- and GM-CSF-derived BMDM did not differ in their ability to kill L929 tumor targets or produce IL-6 and LTC$\sb4$ in response to IFN-γ and LPS. CSF-1-derived BMDM secreted more TNF-α and PGE$\sb2$ at early stages of culture than did GM-CSF-derived BMDM and required only LPS stimulation to produce NO$\sb2\sp-$. In contrast, GM-CSF-derived BMDM secreted NO$\sb2\sp-$ only following treatment with IFN-γ plus LPS. When P815 tumor targets were used, GM-CSF-derived BMDM displayed higher basal and inducible levels of killing than CSF-1-derived BMDM and required only LPS treatment to reach full cytolytic capacity. Additionally, GM-CSF-derived BMDM showed greater listeriacidal capacity than did CSF-1-derived BMDM, particularly following IFN-γ plus LPS treatment. To assess immunocompetence under conditions resembling those of inflammatory sites, BMDM function was examined following treatment with PGE$\sb2$ or in conditions of reduced L-arginine concentration. PGE$\sb2$ (10$\sp{-6}$-10$\sp{-8}$ M) had no effect on BMDM ability to cytolyze L929 cells, kill intracellular Listeria, or produce NO$\sb2\sp-$, but GM-CSF-derived BMDM were inhibited 33% for cytolysis of K562 tumor cells. Interestingly, GM-CSF-derived BMDM were much less sensitive than CSF-1-derived BMDM for PGE$\sb2$, but not cAMP-mediated inhibition of TNF-α. Arginine depletion blocked NO$\sb2\sp-$ production by both BMDM populations and the listeriacidal activity induced by IFN-γ plus LPS was abolished.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Pathobiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2011

Author dc:creator

• Rutherford, Mark Stephen

Contributors dc:contributor

• Shapiro, Stuart Z.

• Biology, Cell
• Health Sciences, Immunology

Statement dc:rights

• Copyright 1991 Rutherford, Mark Stephen

Language dc:language

eng

Identifier

AAI9124479
(UMI)AAI9124479

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/20296