The Cleavage of a Methionyl-Lysyl-Bradykinin-Like Peptide from Kininogen by a Protease of Human Neutrophil Leukocyte Lysosomes
Polymorphonuclear (PMN) leukocytes are essential for the tissue and vascular injury associated with formation and deposition of antigen-antibody complexes (1). There are several mechanisms by which phlogistic agents derived from PMN-leukocyte lysosomes may act. Some act directly, other indirectly by generating vasoactive substances from certain protein substrates. Rabbit leukocytes contain cationic proteins which can act directly on the microcirculation or by releasing vasoactive amines from mast cells (2). These same cells contain acid cathepsins which can generate “leukokinins” from “leukokininogen” at acid pH (3). The acid protease can degrade also basement membrane (4). Basement membrane, elastin and cartilage matrix can be degraded also by a protease of human PMN-leukocytes at neutral pH (5), and collagen by a collagenase (6). By acting on the 3rd and 5th component complement lysates of human PMN-leukocytes can cleave anaphylatoxin-like substances (7, 8). Our own studies indicate that lysates of PMN-leukocyte lysosomes contain a protease capable of cleaving a kinin-like peptide from highly purified kininogen (9). The enzymes were obtained either by fractionating cell lysates or by interacting the cells with antigen-antibody complexes. In the latter case the hydrolases were released into the ambient fluid, and in the cell pellet the phagocytosing and degranulating cells were identified ultrastructurally as neutrophil leukocytes. Subsequently, the enzyme was obtained in partially purified form (10) and in a brief communication we reported on the properties of the highly purified protease with kininogenase activity (11), concluding that it is probably the same protease which degrades elastin, basement membrane and cartilage proteoglycan (5).
KeywordsChloromethyl Ketone Leukocyte Elastase Neutrophil Leukocyte Kinin System Synthetic Kinin
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