DMSO-treated HL60 cells: a model of neutrophil-like cells mainly expressing PDE4B subtype.

The human promyelocytic HL60 cells acquired a neutrophilic phenotype after a 7- to 10-day DMSO treatment. Fc gammaRII was up-regulated. Fc gammaRI was also up-regulated by an additional IFN-gamma treatment. These cells are able to produce O2*- by NADPH oxidase activation in the presence of immune complexes or phorbol-12-myristate-13-acetate (PMA). A change of their PDE4 subtype profile was also observed: PDE4B was the predominant isoenzyme, PDE4D was down-regulated and PDE4A was no longer detectable. Additionally, the more NADPH oxidase was activated by PMA, the less PDE4A was expressed, suggesting that NADPH oxidase activity could be used as a surrogate marker of PDE4A down-regulation. Rolipram and Ariflo (cilomilast), two selective PDE4 inhibitors, dose-dependently inhibited receptor-coupled activation of superoxide. These results suggest that PDE4B is the main subtype involved in regulating superoxide induced by Fc gammaRs activation. Furthermore, these cells, expressing almost exclusively PDE4B subtype, could be useful to identify selective PDE4B inhibitors.

[1]  S. Christensen,et al.  1,4-Cyclohexanecarboxylates: potent and selective inhibitors of phosophodiesterase 4 for the treatment of asthma. , 1998, Journal of medicinal chemistry.

[2]  M. Billah,et al.  Phosphodiesterase 4B2 is the predominant phosphodiesterase species and undergoes differential regulation of gene expression in human monocytes and neutrophils. , 1999, Molecular pharmacology.

[3]  S. Christensen,et al.  1,4‐Cyclohexanecarboxylates: Potent and Selective Inhibitors of Phosphodiesterase 4 for the Treatment of Asthma. , 1998 .

[4]  M. Lindsay,et al.  Role of Arachidonic Acid and Its Metabolites in the Priming of NADPH Oxidase in Human Polymorphonuclear Leukocytes by Peritoneal Dialysis Effluent , 1998, Clinical Diagnostic Laboratory Immunology.

[5]  H. Lübbert,et al.  Expression and regulation of human and rat phosphodiesterase type IV isogenes , 1994, FEBS letters.

[6]  H. Towbin,et al.  Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[7]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[8]  Masahiko Kato,et al.  Role of Cyclic Adenosine Monophosphate in Reducing Superoxide Anion Generation in Guinea Pig Alveolar Macrophages , 1998, Pharmacology.

[9]  M. Houslay,et al.  The multienzyme PDE4 cyclic adenosine monophosphate-specific phosphodiesterase family: intracellular targeting, regulation, and selective inhibition by compounds exerting anti-inflammatory and antidepressant actions. , 1998, Advances in pharmacology.

[10]  W. Nauseef,et al.  Respiratory Burst of Normal Human Eosinophils , 1987, Journal of leukocyte biology.

[11]  R. Vestal,et al.  Effects of selective phosphodiesterase inhibitors on the polymorphonuclear leukocyte respiratory burst. , 1990, The Journal of allergy and clinical immunology.

[12]  A. Doherty.  Phosphodiesterase 4 inhibitors as novel anti-inflammatory agents. , 1999, Current opinion in chemical biology.

[13]  J. A. Badwey,et al.  Release of superoxide and change in morphology by neutrophils in response to phorbol esters: antagonism by inhibitors of calcium-binding proteins , 1985, The Journal of cell biology.

[14]  D. Essayan.  Cyclic nucleotide phosphodiesterase (PDE) inhibitors and immunomodulation. , 1999, Biochemical pharmacology.

[15]  S. Christensen,et al.  The ability of phosphodiesterase IV inhibitors to suppress superoxide production in guinea pig eosinophils is correlated with inhibition of phosphodiesterase IV catalytic activity. , 1995, The Journal of pharmacology and experimental therapeutics.

[16]  C. Bengis-Garber,et al.  Protein kinase A downregulates the phosphorylation of p47 phox in human neutrophils: a possible pathway for inhibition of the respiratory burst. , 1996, Cellular signalling.

[17]  G. P. Livi,et al.  Biochemical characteristics and cellular regulation of phosphodiesterase IV. , 1993, Agents and actions. Supplements.

[18]  J. Oliver,et al.  Superoxide production induced in rabbit polymorphonuclear leukocytes by synthetic chemotactic peptides and A23187. , 1979, The American journal of pathology.

[19]  J. Souness,et al.  Proposal for pharmacologically distinct conformers of PDE4 cyclic AMP phosphodiesterases. , 1997, Cellular signalling.

[20]  C. Anderson,et al.  Biology of Human Immunoglobulin G Fc Receptors , 1991, Journal of leukocyte biology.

[21]  B. Seed,et al.  Isolation and expression of functional high-affinity Fc receptor complementary DNAs. , 1989, Science.

[22]  M. Baggiolini,et al.  Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. , 1989, The Journal of clinical investigation.

[23]  G. Mufti,et al.  Changes in antigen expression on differentiating HL60 cells treated with dimethylsulphoxide, all-trans retinoic acid, alpha1,25-dihydroxyvitamin D3 or 12-O-tetradecanoyl phorbol-13-acetate. , 1998, Leukemia research.

[24]  J. Lambeth,et al.  Diacylglycerol generation and phosphoinositide turnover in human neutrophils: effects of particulate versus soluble stimuli. , 1989, Archives of biochemistry and biophysics.

[25]  Ronald Anderson,et al.  Anti-Oxidative Effects of Theophylline on Human Neutrophils Involve Cyclic Nucleotides and Protein Kinase A , 1998, Inflammation.

[26]  D. Nelson,et al.  Simultaneous Detection of Free Radical Release and Membrane Current during Phagocytosis (*) , 1995, The Journal of Biological Chemistry.

[27]  M. Conti,et al.  Structure and regulation of the rat high-affinity cyclic AMP phosphodiesterases. A family of closely related enzymes. , 1992, Advances in second messenger and phosphoprotein research.

[28]  S. Kuo,et al.  Involvement of cyclic AMP generation in the inhibition of respiratory burst by 2-phenyl-4-quinolone (YT-1) in rat neutrophils. , 1998, Biochemical pharmacology.

[29]  J. Beavo,et al.  Multiple cyclic nucleotide phosphodiesterases. , 1994, Molecular pharmacology.

[30]  J. Corbin,et al.  Cyclic nucleotide phosphodiesterases: relating structure and function. , 2001, Progress in nucleic acid research and molecular biology.

[31]  T. Torphy.  Phosphodiesterase isozymes: molecular targets for novel antiasthma agents. , 1998, American journal of respiratory and critical care medicine.

[32]  J. Satriano,et al.  Activation and attenuation of transcription factor NF-kB in mouse glomerular mesangial cells in response to tumor necrosis factor-alpha, immunoglobulin G, and adenosine 3':5'-cyclic monophosphate. Evidence for involvement of reactive oxygen species. , 1994, The Journal of clinical investigation.

[33]  M. Conti,et al.  Oocyte maturation involves compartmentalization and opposing changes of cAMP levels in follicular somatic and germ cells: studies using selective phosphodiesterase inhibitors. , 1996, Developmental biology.

[34]  V. Lagente,et al.  Effects of interleukin‐10 and modulators of cyclic AMP formation on endotoxin‐induced inflammation in rat lung , 1999, Fundamental & clinical pharmacology.

[35]  J. T. Santinga,et al.  The subcellular particulate NADPH-dependent O2.(-)-generating oxidase from human blood monocytes: comparison to the neutrophil system. , 1982, Blood.

[36]  M. Hulett,et al.  Molecular basis of Fc receptor function. , 1994, Advances in immunology.

[37]  A. Hara,et al.  Tumor necrosis factor-α-mediated signal transduction in human neutrophils: Involvement of sphingomyelin metabolites in the priming effect of tnf-α on the fMLP-stimulated superoxide production , 1999 .

[38]  S. Christensen,et al.  Suppression of human inflammatory cell function by subtype‐selective PDE4 inhibitors correlates with inhibition of PDE4A and PDE4B , 1999, British journal of pharmacology.

[39]  A. Hatzelmann,et al.  Anti-Inflammatory and Immunomodulatory Potential of the Novel PDE 4 Inhibitor Roflumilast in Vitro , 2001 .

[40]  F. DeLeo,et al.  Neutrophils exposed to bacterial lipopolysaccharide upregulate NADPH oxidase assembly. , 1998, The Journal of clinical investigation.

[41]  R. Horowski,et al.  Clinical effects of the neurotropic selective cAMP phosphodiesterase inhibitor rolipram in depressed patients: global evaluation of the preliminary reports , 1985 .

[42]  A. Segal,et al.  Cytochrome b-245 of neutrophils is also present in human monocytes, macrophages and eosinophils. , 1981, The Biochemical journal.

[43]  H. Towbin,et al.  Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. 1979. , 1992, Biotechnology.

[44]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.