Cleavage of the fifth component of complement and generation of a functionally active C5b6-like complex by human leukocyte elastase.
Activation by complement C3/C5 convertases of the fifth component of human complement, C5, leads to two active cleavage products: C5a, a chemotactic peptide, and C5b, the activated form of C5. Human leukocyte elastase (HLE) has long been known to also release from C5 a chemotactic, C5a-like fragment. This, however, cannot be identical with C5a, since HLE does not cleave peptide bonds at the carboxyl group of arginine, the cleavage site that separates C5a and C5b after the exposure to the complement convertases. Therefore, the question arose whether HLE is capable of releasing a functionally C5b-like product from C5. The results show that this is, indeed, so. Treatment of human C5 with HLE in the presence of C6 leads to the formation on an active C5b6-like complex that lyses non-sensitized guinea pig red cells upon addition of the terminal components C7, C8, and C9. However, since C6 is highly sensitive to the hydrolytic action of HLE, the yield of the activation complex is rather low. The results offer a third possibility for the activation of C5: 1) classical cleavage at Arg74 by complement convertases, 2) oxidation of methionine residues without cleavage, and, as shown here, 3) cleavage by elastase at (a) site(s) distal from Arg74. The three procedures may modulate the relative yield of the two activities generated from C5, C5a-like and C5b-like effects.
Vogt
W
W
Max Planck Institut für Experimentelle Medizin, Göttingen, Germany.
D000818:Animals; D003182:Complement C5 / Q000378:metabolism; D003183:Complement C6 / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism
D003182:Complement C5; D003183:Complement C6; C050974:complement C5b-6 complex; D003165:Complement System Proteins; D019272:Leukocyte Elastase; D014357:Trypsin