EOSINOPHIL GRANULE PROTEINS ARE SELECTIVE ACTIVATORS OF HUMAN HEART MAST-CELLS

Eosinophilia in humans is associated with eosinophil infiltration and cardiac localization of eosinophil granule proteins. Eosinophil cation ic proteins are responsible for cardiac disease in some patients with eosinophilia. We have investigated the in vitro effect of four eosinop hil granule proteins: eosinophil cationic protein (ECP)? major basic p rotein (MBP), eosinophil-derived neurotoxin (EDN) and eosinophil perox idase (EPO), on mast cells isolated from human cardiac tissue (HHMC). ECP and, to a lesser extent MBP (0.3-3 mu M), but not EDN and EPO, sti mulated the release of histamine and tryptase from HHMC. This release reaction induced by ECP and MBP was Ca2+- and temperature-dependent an d was abolished by preincubation with anti-ECP and anti-MBP, respectiv ely. The activation of HHMC by ECP and MBP was abolished by preincubat ion with 2-deoxy-D-glucose and antimycin A. These data demonstrate tha t some eosinophil cationic proteins, ECP and MBP, are selective activa tors of HHMC, thus contributing to the cardiac lesions in patients wit h eosinophilia.