Assessment of histamine release and kinin formation in man: identification of kinin degradation products and characterization of a lymphocyte-dependent histamine releasing factor.

Factors traditionally associated with histamine release include IgE antibody plus antigen and the anaphylatoxins C3a, C4a, and C5a. Yet histamine release is thought to occur in disorders such as chronic urticaria, atopic dermatitis, and contact dermatitis in which the above mechanisms do not appear operative. We have partially purified a factor from stimulated human mononuclear cells which causes basophil histamine release. It is homogeneous by gel filtration with a molecular weight of about 35,000 daltons and has two molecular forms when assessed by ion exchange chromatography, isoelectrofocusing in gels and chromatofocusing. The purified material, when radiolabeled, gives a single band upon two-dimensional gel electrophoresis and radioautography. This factor may therefore represent one mechanism in which delayed hypersensitivity and histamine release are linked. We are also developing methods to better assess the kinin-forming system in allergic diseases. Assays for enzyme inhibitor complexes are the most sensitive and specific methods for inferring activation in plasma. These include quantitation of activated Hageman factor-C1 INH complexes and kallikrein-C1 INH complexes each of which appears elevated in cutaneous late-phase reactions. However, bradykinin assessment is fraught with difficulties including spurious generation and rapid inactivation. Using high performance liquid chromatography we have separated bradykinin from kallidin, des-Arg9-bradykinin (the degradation product of carboxypeptidase N) as well as the fragments Arg-Pro-Pro-Gly-Phe, Ser-Pro, and Phe-Arg, the degradation products formed by angiotensin-converting enzyme. These can be assayed in purified mixtures, can be detected upon addition of bradykinin to human plasma and are formed by kaolin treatment of plasma.