title: Differentiation of human monocytes in vitro with granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor produces distinct changes in cGMP phosphodiesterase expression.
abstract: The cytokines macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) promote differentiation of monocytes into macrophages with distinct phenotypes and unique functional abilities. In this report, we characterize how monocytes and macrophages differentiated from monocytes with M-CSF and GM-CSF regulate their cGMP levels by controlling which phosphodiesterases (PDEs) and guanylyl cyclases (GCs) are expressed. We find that PDE1B and PDE2A are expressed at low levels in monocytes, but are the major cGMP PDEs expressed in macrophages. M-CSF differentiation triggers increased expression of PDE1B and PDE2A, while GM-CSF causes a large increase only in PDE1B. Based on PDE expression, we identified THP-1 and U937 cell lines as possible models for studying the roles of PDE1B and PDE2A in macrophage function. We additionally characterized changes in expression of GCs upon differentiation. We found that GM-CSF differentiation triggers a small decrease in soluble guanylyl cyclase (sGC) and a large increase in GC-A, while M-CSF significantly decreases sGC.
authors.affiliation: Department of Pharmacology, University of Washington Medical School, Box 357280, Seattle, WA 98195-7280, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Bender
authors.forename: Cari L
authors.initials: CL
authors.lastname: Ostenson
authors.forename: Daniela
authors.initials: D
authors.lastname: Giordano
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Beavo
mesh_terms: D018929:Cell Culture Techniques; D002454:Cell Differentiation; D006152:Cyclic GMP / Q000378:metabolism*; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D020033:Protein Isoforms; D020298:U937 Cells
chemical_list: D020033:Protein Isoforms; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010727:Phosphoric Diester Hydrolases; D006162:Guanylate Cyclase; D006152:Cyclic GMP