Desensitization induces hyporesponsiveness and cell-surface phenotype changes on wild-type and humanized mouse mast cells

Abstract

Background Rapid drug desensitization (DST) protocols have been developed based on clinical evidence, but in vitro studies are lacking. Understanding the mechanisms involved in the early stages of DST will allow improvements in patients’ treatment. The aim of this study is to demonstrate and characterize the induction of hyporesponsiveness in murine mast cells by desensitization. Methods We assessed the effect of rapid desensitization on murine bone marrow derived mast cells (BMMC). Experiments with three diferent types of murine BMMC were done: wild-type, LILRB4-/-, and transgenic expressing the human receptor FceRI. Wild-type and LILRB4-/- BMMC were sensitized with anti-DNP IgE and stimulated with DNP, while transgenic BMMC were sensitized with concentrated human serum of allergic subjects and stimulated with the respective allergen. BMMC were stimulated through desensitization or single activation, with optimal or suboptimal doses of antigen. Comparisions were made according to the percentage of b-Hexosaminidase (b-Hex) release by BMMC and the expression of LAMP-1 on the surface of these cells. Furthermore, expression of FceRI, PDL1 and LILRB4 on the surface of BMMC were also assessed. Results