Mechanism of kinin release from human low-molecular-mass-kininogen by the synergistic action of human plasma kallikrein and leukocyte elastase.
We have investigated the kinin release from human L-kininogen, a poor substrate for plasma kallikrein, by the synergistic action of human PMN elastase and plasma kallikrein. Although PMN elastase alone failed to generate kinin activity from L-kininogen, combination of PMN elastase with plasma kallikrein was found to be effective for the generation of kinin activity from L-kininogen. Two kinds of kinin, bradykinin and Met-Lys-bradykinin, were found to be released from L-kininogen by the synergistic action of PMN elastase and plasma kallikrein. Pretreatment of L-kininogen with PMN elastase facilitated the kinin release by plasma kallikrein, whereas pretreatment of L-kininogen with plasma kallikrein did not allow kinin release by the action of PMN elastase. These results suggested that PMN elastase would act firstly on L-kininogen to form a kinin containing fragment, from which kinin is released by the action of plasma kallikrein. The kinin-containing fragment was isolated by gel filtration and high-performance liquid chromatography of the elastase digest of L-kininogen. The amino-acid analysis and N-terminal amino-acid sequence analysis revealed that the kinin-containing fragment consisted of 26 amino-acid residues and is formed by cleavage of an Ile-Ser and a Ser-His bond of L-kininogen.
Sato
F
F
Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
Nagasawa
S
S
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D006801:Humans; D007610:Kallikreins / Q000097:blood / Q000502:physiology*; D007700:Kinetics; D007704:Kininogens / Q000378:metabolism*; D007705:Kinins / Q000302:isolation & purification / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000097:blood*; D012463:Saliva / Q000201:enzymology
D000596:Amino Acids; D007704:Kininogens; D007705:Kinins; D007610:Kallikreins; D010196:Pancreatic Elastase