Biology Reference
In-Depth Information
Cyclic Nucleotides and Phosphodiesterases
in Monocytic Differentiation
Angie L. Hertz and Joseph A. Beavo
Contents
1 Introduction ...................................................................................... 366
2 Macrophage Differentiation .................................................................... 367
2.1 HL-60 ..................................................................................... 367
2.2 U937 ...................................................................................... 370
2.3 Human AB Serum and M-CSF ......................................................... 372
2.4 GM-CSF . . ................................................................................ 374
3 Dendritic Cell Differentiation .................................................................. 376
4 Osteoclast Differentiation ...................................................................... 380
5 Murine Bone Marrow Differentiation ......................................................... 383
6 Conclusions ...................................................................................... 384
References . . . .........................................................................................385
Abstract Monocytes are immune cells that can differentiate into a number of cell
types including macrophages, dendritic cells, and osteoclasts upon exposure to
various cytokines. The phenotypes of these differentiated cells are highly heteroge-
neous and their differentiation can be affected by the cyclic nucleotides, 3
0
-5
0
-cyclic
adenosine monophosphate (cAMP) and 3
0
-5
0
-cyclic guanosine monophosphate
(cGMP). The intracellular levels of cAMP and cGMP are controlled through regu-
lation of production by adenylyl and guanylyl cyclases and through degradation by
cyclic nucleotide phosphodiesterases (PDEs). PDE inhibition and subsequent changes
in cyclic nucleotide levels can alter the final phenotype of a differentiating monocyte
with regards to surface marker expression, gene expression, or changes in secreted
chemokine and cytokine levels. The differentiation process itself can also be either
inhibited or augmented by changes in cyclic nucleotide levels, depending on the
system being studied and the timing of cyclic nucleotide elevation. This chapter
A.L. Hertz and J.A. Beavo (
*
)
Department of Pharmacology, School of Medicine, University of Washington, P.O. Box 357280,
Seattle, WA 98125, USA
e-mail: alhertz@uw.edu; beavo@uw.edu
