Bacterial immunoglobulin superantigen proteins A and L activate human heart mast cells by interacting with immunoglobulin E

Human heart mast cells (HHMC) have been identified in heart tissue, perivas cularly, and in the intima of coronary arteries. In vitro activation of iso lated HHMC induces the release of vasoactive and proinflammatory mediators (histamine, tryptase, and cysteinyl leukotriene C-4 [LTC4]). We investigate d the effects of several bacterial proteins on HHMC activation in vitro. HH MC released histamine, tryptase, and LTC4 in response to Staphylococcus aur eus Cowan 1 and the immunoglobulin (Ig)-binding protein A, but not to S. au reus Wood 46, which does not synthesize protein A. The effect of protein A was inhibited by preincubation with monoclonal IgM V(H)3(+). Some strains o f Peptostreptococcus magnus express an Ig light chain-binding surface prote in called protein L. Such bacteria and soluble protein L stimulated the rel ease of preformed and newly synthesized mediators from HHMC. Preincubation of HHMC with either protein A or protein L resulted in complete cross-desen sitization to a subsequent challenge with the heterologous stimulus or anti -IgE. Monoclonal IgE (kappa chains) blocked protein L-induced release, wher eas IgE (lambda chains) had no effect. Streptococcal protein G, formyl-cont aining tripeptide, and pepstatin A did not activate HHMC. Bacterial product s protein A and protein L and intact bacteria (S. aureus and P. magnus) act ivate HHMC by acting as Ig superantigens.