Phosphodiesterase III inhibition affects platelet-monocyte aggregate formation depending on the axis of stimulation.
OBJECTIVE
The purpose of this study was to investigate the effect of the phosphodiesterase (PDE) type 3 inhibitor milrinone on the adhesion of platelets to monocytes in vitro.


METHODS
Prospective study.


METHODS
University experimental laboratory.


METHODS
Ten healthy volunteers.


METHODS
Whole blood was incubated with 1, 10, or 100 micromol/L of milrinone. After stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP) or adenosine-5-diphosphate (ADP), platelet-monocyte adhesion and CD11b, PSGL-1, GPIIb/IIIa, and P-selectin expression were measured by flow cytometry.


RESULTS
The formation of platelet-monocyte conjugates after PDE3 inhibition depended on the type of stimulation. In unstimulated and FMLP-stimulated blood platelet monocytes, aggregation was enhanced by increasing concentrations of milrinone. This augmentation was accompanied by a rise in P-selectin expression in platelets. In ADP-stimulated blood the number of platelet-monocyte aggregates decreased with increasing concentrations of milrinone. Concurrent with the reported antiinflammatory properties of PDE-inhibition, an inhibition of CD11b expression was found in monocytes after stimulation with FMLP. In contrast, in unstimulated samples lower concentrations of milrinone caused an increase in CD11b.


CONCLUSIONS
These findings suggest that the effects of PDE3 inhibition on platelets and monocytes are modified by the type of stimulation and only partially suppress the inflammatory response of platelets and monocytes. The increase in platelet-monocyte conjugates in unstimulated and FMLP-stimulated blood suggested that PDE3 inhibition may also trigger proinflammatory reactions.
Horn
Nicola A
NA
Department of Anesthesiology, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany. n.horn@anes.umcn.nl
Anastase
Denisa M
DM
Hecker
Klaus E
KE
Baumert
Jan H
JH
Scheffer
Gert J
GJ
Rossaint
Rolf
R
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D039481:CD11b Antigen / Q000096:biosynthesis; D002448:Cell Adhesion / Q000187:drug effects; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D020105:Milrinone / Q000494:pharmacology*; D009000:Monocytes / Q000502:physiology*; D019007:P-Selectin / Q000096:biosynthesis; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000096:biosynthesis; D011446:Prospective Studies
D039481:CD11b Antigen; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D010726:Phosphodiesterase Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D020105:Milrinone