PMID- 32425769
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 11
DP  - 2020
TI  - PDE3 Inhibition Reduces Epithelial Mast Cell Numbers in Allergic Airway 
      Inflammation and Attenuates Degranulation of Basophils and Mast Cells.
PG  - 470
LID - 10.3389/fphar.2020.00470 [doi]
LID - 470
AB  - Epithelial mast cells are generally present in the airways of patients with 
      allergic asthma that are inadequately controlled. Airway mast cells (MCs) are 
      critically involved in allergic airway inflammation and contribute directly to 
      the main symptoms of allergic patients. Phosphodiesterase 3 (PDE3) tailors 
      signaling of cyclic adenosine monophosphate (cAMP) and cyclic guanosine 
      monophosphate (cGMP), which are critical intracellular second messenger molecules 
      in various signaling pathways. This paper investigates the pathophysiological 
      role and disease-modifying effects of PDE3 in mouse bone marrow-derived MCs 
      (bmMCs), human LAD2- and HMC1 mast cell lines, human blood basophils, and 
      peripheral blood-derived primary human MCs (HuMCs). In a chronic house dust mite 
      (HDM)-driven allergic airway inflammation mouse model, we observed that PDE3 
      deficiency or PDE3 inhibition (PDE3i) therapy reduced the numbers of epithelial 
      MCs, when compared to control mice. Mouse bone marrow-derived MCs (bmMCs) and the 
      human HMC1 and LAD2 cell lines predominantly expressed PDE3B and PDE4A. BmMCs 
      from Pde3(-/-) mice showed reduced loss of the degranulation marker CD107b 
      compared with wild-type BmMCs, when stimulated in an immunoglobulin E 
      (IgE)-dependent manner. Following both IgE-mediated and substance P-mediated 
      activation, PDE3i-pretreated basophils, LAD2 cells, and HuMCs, showed less 
      degranulation than diluent controls, as measured by surface CD63 expression. MCs 
      lacking PDE3 or treated with the PDE3i enoximone exhibited a lower calcium flux 
      upon stimulation with ionomycine. In conclusion PDE3 plays a critical role in 
      basophil and mast cell degranulation and therefore its inhibition may be a 
      treatment option in allergic disease.
CI  - Copyright (c) 2020 Beute, Ganesh, Nastiti, Hoogenboom, Bos, Folkerts, Schreurs, 
      Hockman, Hendriks and KleinJan.
FAU - Beute, Jan
AU  - Beute J
AD  - Department of Pulmonary Medicine, Erasmus MC, Rotterdam, Netherlands.
FAU - Ganesh, Keerthana
AU  - Ganesh K
AD  - Department of Pulmonary Medicine, Erasmus MC, Rotterdam, Netherlands.
FAU - Nastiti, Hedwika
AU  - Nastiti H
AD  - Department of Pulmonary Medicine, Erasmus MC, Rotterdam, Netherlands.
FAU - Hoogenboom, Robin
AU  - Hoogenboom R
AD  - Department of Pulmonary Medicine, Erasmus MC, Rotterdam, Netherlands.
FAU - Bos, Vivica
AU  - Bos V
AD  - Department of Pulmonary Medicine, Erasmus MC, Rotterdam, Netherlands.
FAU - Folkerts, Jelle
AU  - Folkerts J
AD  - Department of Pulmonary Medicine, Erasmus MC, Rotterdam, Netherlands.
FAU - Schreurs, Marco W J
AU  - Schreurs MWJ
AD  - Department of Immunology, Erasmus MC, Rotterdam, Netherlands.
FAU - Hockman, Steve
AU  - Hockman S
AD  - Flow Cytometry Core of the National Heart, Lung, and Blood Institute, NIH, 
      Bethesda, MD, United States.
FAU - Hendriks, Rudi W
AU  - Hendriks RW
AD  - Department of Pulmonary Medicine, Erasmus MC, Rotterdam, Netherlands.
FAU - KleinJan, Alex
AU  - KleinJan A
AD  - Department of Pulmonary Medicine, Erasmus MC, Rotterdam, Netherlands.
LA  - eng
PT  - Journal Article
DEP - 20200501
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC7206980
OTO - NOTNLM
OT  - PDE3
OT  - PDE4
OT  - allergic airway
OT  - animal model
OT  - asthma
OT  - enoximone
OT  - house dust mite
OT  - inflammation
EDAT- 2020/05/20 06:00
MHDA- 2020/05/20 06:01
PMCR- 2020/05/01
CRDT- 2020/05/20 06:00
PHST- 2019/12/07 00:00 [received]
PHST- 2020/03/25 00:00 [accepted]
PHST- 2020/05/20 06:00 [entrez]
PHST- 2020/05/20 06:00 [pubmed]
PHST- 2020/05/20 06:01 [medline]
PHST- 2020/05/01 00:00 [pmc-release]
AID - 10.3389/fphar.2020.00470 [doi]
PST - epublish
SO  - Front Pharmacol. 2020 May 1;11:470. doi: 10.3389/fphar.2020.00470. eCollection 
      2020.