Protein L: A bacterial Ig-binding protein that activates human basophils and mast cells

Peptostreptococcus magnus strain 312 (10⁶ to 10⁸/ml), which synthesizes a protein capable of binding to κ L chains of human Ig (protein L), stimulated the release of histamine from human basophils in vitro. P. magnus strain 644, which does not synthesize protein L, did not induce histamine secretion. Soluble protein L (3 × 10^-2 to 3 Mg/ml) induced histamine release from human basophils. The characteristics of the release reaction were similar to those of rabbit IgG anti-Fc fragment of human IgE (anti-IgE): it was Ca²⁺- and temperature-dependent, optimal release occurring at 37°C in the presence of 1.0 mM extracellular Ca²⁺. There was an excellent correlation (r = 0.82; p <0.001) between the maximal percent histamine release induced by protein L and that induced by anti-IgE, as well as between protein L and protein A from Staphylococcus aureus (r = 0.52; p <0.01). Preincubation of basophils with either protein L or anti-IgE resulted in complete cross-desensitization to a subsequent challenge with the heterologous stimulus. IgE purified from myeloma patients PS and PP (λ-chains) blocked anti-IgE-induced histamine release but failed to block the histamine releasing activity of protein L. In contrast, IgE purified from myeloma patient ADZ (κ-chains) blocked both anti-IgE- and protein L-induced releases, whereas human polyclonal IgG selectively blocked protein L-induced secretion. Protein L acted as a complete secretagogue, i.e., it activated basophils to release sulfidopeptide leukotriene C₄ as well as histamine. Protein L (10^-1 to 3 μg/ml) also induced the release of preformed (histamine) and de novo synthesized mediators (leukotriene C₄ and/or PGD₂) from mast cells isolated from lung parenchyma and skin tissues. Intradermal injections of protein L (0.01 to 10 μg/ml) in nonallergic subjects caused a dose-dependent wheal-and-flare reaction. Protein L activates human basophils and mast cells in vitro and in vivo presumably by interacting with κ L chains of the IgE isotype.