Revising Cromolyn Sodium Effect On Mouse And Muman Mast Cells

Pier Giorgio Puzzovio ¹ Thayse Bruggerman Thayse Bruggerman ² Hadas Pahima ¹ David Mankuta ³ Bruce D. Levy ² Francesca Levi-Schaffer ¹

¹Pharmacology and Experimental Therapeutics Unit, School of Pharmacy, Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Israel
²Pulmonary and Critical Care Medicine, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, USA
³Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center, Israel

Cromolyn sodium (CS) has been extensively described as a mast cells (MCs) stabilizer for its ability to impair mediators release, specifically histamine, in human, murine and rat MCs. Because of this effect, it was employed as an anti-allergic drug. However, its mechanism of action is still poorly understood.

We aimed to further characterize CS effect in vitro on human cord blood-derived MCs (CBMCs) and murine bone marrow-derived MCs (BMMCs) and in vivo in murine models of allergic inflammation (AI).

CBMCs and BMMCs were incubated with CS and activated via IgE-mediated activation. Pro-inflammatory and pro-resolutory effectors were followed. Allergic peritonitis (AP) was induced in Wild Type (WT) mice by OVA/SEB subcutaneous sensitizations and OVA/SEB intraperitoneal challenge. Asthma was induced in WT mice byintranasal House Dust Mite (HDM) sensitizations and challenges. CS was daily administered intraperitoneally after the challenge until euthanasia. Mice were euthanized at different time points and disease characteristics were analysed.

CS did not affect neither tryptase nor IL-8 release, but it significantly increased CD300a expression and IL-10 release from CBMCs. CD300a expression on C57BL-BALB/c BMMCs was not significantly affected by CS. In the AP model, total cells and eosinophil (Eos) numbers were significantly reduced, while IL-10 was increased, by CS treatment. Peritoneal lavages tryptase levels did not change significantly. HDM-challenged mice presented with a trend of reduced total cell and Eos numbers in the bronchoalveolar lavage and in the lungs.

Our results point out an anti-inflammatory, rather than stabilizing, CS effect via modulation of pro-resolutory effectors on MCs.