A Biochemical and Functional Assessment of Monocyte Phosphodiesterase Activity in Healthy and Asthmatic Subjects

Identification and quantification of phosphodiesterase 4 subtypes in CD4 and CD8 lymphocytes from healthy and asthmatic subjects

“…No significant difference was found when comparing the two groups. These data extend our previous observations that despite an increased overall PDE activity in inflammatory cells obtained from patients with asthma compared to cells obtained from healthy subjects, there was no altered PDE4 activity or altered sensitivity to PDE4 inhibitors with respect to proliferation or TNFα release ( Landells et al ., 2000 ). These results differ markedly from studies with cells isolated from the peripheral blood of patients with atopic dermatitis ( Banner et al ., 1995 ; Hanifin et al ., 1996 ).…”

“…A large body of evidence exists which suggests PDE activity may be altered in cells obtained from patients with atopic dermatitis ( Banner et al ., 1995 ) and it has previously been demonstrated that cyclic AMP PDE activity is elevated in leukocytes from individuals with atopic dermatitis ( Grewe et al ., 1982 ), suggested to be secondary to the expression of a novel PDE isoenzyme ( Chan et al ., 1993 ). Similarly, lymphocyte PDE activity was augmented in lymphocytes from asthmatic compared to healthy subjects ( Tohda et al ., 1998 ) and we have recently extended these findings ( Landells et al ., 2000 ). However, some studies have demonstrated that cyclic AMP and cyclic GMP PDE activities, and isoenzyme profiles are similar in CD4 + and CD8 + T lymphocyte homogenates of healthy and atopic subjects ( Tenor et al ., 1995 ; Gantner et al ., 1997 ).…”

“…Increased PDE4A and PDE4B2 expression was observed in CD4 + cells from atopic subjects, although this did not appear to result in significantly higher cyclic AMP PDE activity ( Gantner et al ., 1997 ). However, it is not yet known which PDE4 subtypes are present in the inflammatory cells of patients with atopic asthma, but it is plausible that differential expression of these isoenzyme subtypes may contribute to the increased PDE activity that has been observed in inflammatory cells isolated from patients with asthma ( Tohda et al ., 1998 ; Landells et al ., 2000 ). Currently, much research is being undertaken to develop novel PDE4 inhibitors for the treatment of inflammatory conditions including asthma and a greater understanding of PDE4 subtype expression profiles in inflammatory cells from asthmatic patients may encourage further research and would provide new insight into the causes of the exaggerated immune responses observed in these individuals.…”

Characteristic DNA methylation profiles in peripheral blood monocytes are associated with inflammatory phenotypes of asthma

“…21 This depletion of cAMP in monocytes has been associated with asthma. 22 It is now well recognized that increases in the cAMP in these cells have a potent anti-inflammatory action, such as inhibition of pro-inflammatory cytokine production and enhanced expression of anti-inflammatory IL-10. 24 The synthesis of cAMP is regulated by the ADCY gene family and one of these genes, ADCY8, occupied a central node in our data.…”

“…Phosphodiesterases (PDEs) catalyzed the hydrolysis of cAMP; increased PDE expression has been attributed to aggravated asthma and allergy symptoms. 22,35 Among the 11 PDEs identified to date, PDE4, PDE7, and PDE8 are selective for cAMP. The PDE4 family consists of 4 isoforms (A, B, D, and D), of which PDE4B is predominantly expressed in monocytes and neutrophils.…”