RBL-2H3 and primary mast cells and their use in screening novel anti-inflammatory compounds

Abstract

Mast cells (MC) have been mainly studied as key effectors in allergic diseases and inflammatory conditions such hypersensitivity reactions, asthma, atopic dermatitis and multiple sclerosis. Following the crosslinkage of membraneous FcεRI, by antigens, a large number of chemical mediators are secreted. This event leads to the recruitment and activation of basophils and eosinophils that sustain the inflammatory response. The role of mast cells, however, is not limited to the initiation of allergic response but they are also fundamental players in the innate immune response; for example they can be activated directly by pathogens through a family of pattern recognition receptors called ‘’Toll-like receptors” (TLRs). In particular, TLR2 and 4 seem to be crucial to the mast cell response to pathogens. In rodents, mast cells respond to lipopolysaccharide through their TLR4s by the release of pro-inflammatory cytokines without concurrent degranulation or they can degranulate following peptidoglycan challenge through a TLR2- mediated pathway. As part of an ongoing study to identify novel molecules with therapeutic potential, we examined the effect of two diastereoisomers (PH2 and PH5) and their four enantiomers (PH3, PH4, PH21 and PH22) of an indane compound, 2-benzyl-2,3-dihydro-1H-1'H-2,2’-biinden-1- ol, on the degranulation of freshly harvested rat peritoneal mast cells (RPMC) and on the rat basophilic leukaemia mast cell line, RBL-2H3 stimulated with a variety of stimuli (both immunological and non- immunological).