Anaphylactic release of a prekallikrein activator from human lung in vitro.
We have demonstrated the in vitro IgE-mediated release of a prekallikrein activator from human lung. The lung prekallikrein activator was partially purified by sequential chromatography on sulfopropyl-Sephadex, DEAE-Sephacel, and Sepharose 6B. Purified human prekallikrein was converted to its active form (kallikrein) by the lung protease. The generated kallikrein was shown to be biologically active; that is, it generates bradykinin from purified human high-molecular weight kininogen and also cleaves benzoyl-propyl-phenyl-arginyl-p-nitroanilide, a known synthetic substrate of kallikrein. The lung prekallikrein activator differs from the known physiologic activators of prekallikrein (the activated forms of Hageman factor) with respect to: (a) size (it has a mol wt of approximately 175,000); (b) synthetic substrate specificity (D-propyl/phenyl/arginyl-p-nitroanilide is a substrate for the activated forms of Hageman factor, but not the lung protease); (c) antigenic specificity (an anti-Hageman factor immunoadsorbent column did not remove significant amounts of the lung protease, while it removed most of the activity of activated Hageman factor fragments); and (d) inhibition profile (the lung proteases was not inhibited by corn trypsin inhibitor). This prekallikrein activator provides a physiologic mechanism by which prekallikrein can be directly activated during IgE-mediated reactions of the lung. While the role of this lung prekallikrein activator in immediate hypersensitivity reactions and in other inflammatory processes is not clear, it does represent a first and important interface between IgE-mediated reactions and the Hageman factor-dependent pathways of the inflammatory response.
D000707:Anaphylaxis / Q000201:enzymology*; D002852:Chromatography, Ion Exchange; D000939:Epitopes; D005174:Factor XII / Q000032:analysis / Q000276:immunology / Q000302:isolation & purification*; D015956:Factor XIIa; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D007163:Immunosorbent Techniques; D008168:Lung / Q000201:enzymology* / Q000276:immunology; D008970:Molecular Weight; D010446:Peptide Fragments / Q000032:analysis / Q000302:isolation & purification*; D010447:Peptide Hydrolases / Q000378:metabolism; D013379:Substrate Specificity
D000939:Epitopes; D010446:Peptide Fragments; D007073:Immunoglobulin E; D005174:Factor XII; D010447:Peptide Hydrolases; D015956:Factor XIIa