Cromolyn Sodium differentially regulates human mast cell and mouse leukocyte responses to control allergic inflammation

Pier Giorgio Puzzovio, Thayse R. Brüggemann, Hadas Pahima, David Mankuta, Bruce D. Levy, Francesca Levi-Schaffer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Background: Cromolyn Sodium (CS) has been used in the past as an anti-allergy drug owing to its mast cell (MC) stabilizing properties that impair histamine release. However, additional mechanisms for its clinical actions are likely and might help to identify new roles for MCs and leukocytes in regulating inflammation. Here, using human cord blood-derived MCs (CBMCs), mouse bone marrow-derived MCs (BMMCs) and eosinophils (BMEos), and in vivo mouse models of allergic inflammation (AI), additional actions of CS on MCs were determined. Methods: The in vitro effects of CS on IgE-activated human and mouse MCs were assessed by measuring the levels of pro-inflammatory (tryptase, LTC4, IL-8, CD48) and pro-resolution effectors (IL-10, CD300a, Annexin A1) before and after CS treatment. The in vivo effects of daily CS injections on parameters of inflammation were assessed using mouse models of allergic peritonitis (AP) (Ovalbumin/Alum- or Ovalbumin/S. aureus enterotoxin B) and allergic airways inflammation (AAI) (house dust mite (HDM)). Results: In vitro, CS did not affect pro-inflammatory effectors but significantly increased the anti-inflammatory/pro-resolution CD300a levels and IL-10 release from IgE-activated CBMCs. BMMCs were not affected by CS. In vivo, CS injections decreased total cell and Eos numbers in the peritoneal cavity in the AP models and bronchoalveolar lavage and lungs in the AAI model. CS reduced EPX release from PAF-activated BMEos in vitro, possibly explaining the in vivo findings. Conclusion: Together, these results demonstrate immunomodulatory actions for CS in AI that are broader than only MC stabilization.

Original languageAmerican English
Article number106172
JournalPharmacological Research
Volume178
DOIs
StatePublished - Apr 2022

Bibliographical note

Funding Information:
This study was funded by grants from the United States-Israel Binational Science Foundation BSF 2015045 (FLS, BDL), Rosetrees Trust UK (FLS), The Aimwell Charitable Trust (FLS), Emalie Gutterman Memorial Endowed Fund USA (FLS) and US National Institutes of Health Grants R01HL122531 and P01GM095467 (BDL). FLS is affiliated with the Adolph and Klara Brettler Center for Molecular Pharmacology and Therapeutics at the School of Pharmacy of The Hebrew University of Jerusalem.

Funding Information:
This study was funded by grants from the United States-Israel Binational Science Foundation BSF 2015045 (FLS, BDL), Rosetrees Trust UK (FLS), The Aimwell Charitable Trust (FLS), Emalie Gutterman Memorial Endowed Fund USA (FLS) and US National Institutes of Health Grants R01HL122531 and P01GM095467 (BDL). FLS is affiliated with the Adolph and Klara Brettler Center for Molecular Pharmacology and Therapeutics at the School of Pharmacy of The Hebrew University of Jerusalem.

Publisher Copyright:
© 2022 Elsevier Ltd

Keywords

  • Allergic inflammation
  • Cromolyn Sodium
  • Cytokines
  • Eosinophils
  • Mast cells
  • Ovalbumin
  • Interleukin-10
  • Humans
  • Immunoglobulin E
  • Cromolyn Sodium/pharmacology
  • Leukocytes
  • Animals
  • Inflammation/drug therapy
  • Mice
  • Staphylococcus aureus
  • Mast Cells

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