NDLI: Type 4A cAMP-specific phosphodiesterase is stored in granules of human neutrophils and eosinophils

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Type 4A cAMP-specific phosphodiesterase is stored in granules of human neutrophils and eosinophils

Content Provider	Springer Nature Link
Author	Pryzwansky, Katherine B. Madden, Victoria J.
Copyright Year	2003
Abstract	Persistent elevations of cAMP levels are generally accompanied by an inhibition of granulocyte functions. Phosphodiesterases play a critical role in regulating intracellular levels of cAMP. The expression of three isoforms of type 4 cAMP-specific phosphodiesterase (PDE4) in neutrophils suggests diversity of isoform localization and targeting in regulating cell function. The sites of cAMP regulation in granulocytes by the PDE4A isoform were investigated by immunoelectron microscopy. PDE4A was localized uniformly in all granule classes of eosinophils, but was restricted in neutrophils to a subset of myeloperoxidase (MPO)-containing granules that were round or elongated with a central crystalloid core. Granulocytes were stimulated with fMLP to investigate the sites of PDE4A targeting during cell activation. In neutrophils, fMLP induced a rapid (1 min) translocation of granules containing PDE4A to the plasmalemma, where some PDE4A and MPO were exocytosed. In these cells, PDE4A labeling within granules was focal and no longer homogeneous. While immunogold labeling of PDE4A was reduced after fMLP stimulation, staining of MPO-containing granules remained high. Extracellular release of PDE4A was also observed in eosinophils stimulated with fMLP. Morphometry revealed that Au labeling was significantly reduced within 1 min, and that there was a shift in PDE4A localization within eosinophil granules from the crystalline core to the matrix. Fluctuations of cAMP levels and ectoprotein kinase activity with PKA properties occur in blood under normal and pathological conditions. The exclusive localization of PDE4A within granules of neutrophils and eosinophils suggests that PDE4A may function to downregulate cAMP signaling at the cell membrane and/or in the extracellular space at the time of granule release.
Starting Page	301
Ending Page	311
Page Count	11
File Format	PDF
ISSN	0302766X
Journal	Cell and Tissue Research
Volume Number	312
Issue Number	3
e-ISSN	14320878
Language	English
Publisher	Springer-Verlag
Publisher Date	2003-05-23
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Immunogold cAMP-dependent protein kinase fMLP Myeloperoxidase Lactoferrin Human
Content Type	Text
Resource Type	Article
Subject	Cell Biology Histology Pathology and Forensic Medicine

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