CLEAVAGE OF HUMAN-COMPLEMENT COMPONENT C5 BY CYSTEINE PROTEINASES FROM PORPHYROMONAS (BACTEROIDES) GINGIVALIS - PRIOR OXIDATION OF C5 AUGMENTS PROTEINASE DIGESTION OF C5
Rg. Discipio et al., CLEAVAGE OF HUMAN-COMPLEMENT COMPONENT C5 BY CYSTEINE PROTEINASES FROM PORPHYROMONAS (BACTEROIDES) GINGIVALIS - PRIOR OXIDATION OF C5 AUGMENTS PROTEINASE DIGESTION OF C5, Immunology, 87(4), 1996, pp. 660-667
Since severe periodontitis is characterized by an acute inflammatory r
esponse with cellular infiltration and microbial overgrowth, plasma pr
oteins could be exposed to both proteinases and oxidants released from
the granulocytes, as well as to proteinases from the microorganisms.
When human complement component C5 was digested by cysteine proteinase
s (i.e. gingipain-R and gingipain-K) from Porphyromonas gingivalis, li
mited cleavage of the C5 molecule was observed. If C5 was first oxidiz
ed by hydroxyl radicals, these gingipains converted modified C5 to fra
gments that exhibited significantly greater pro-inflammatory activity
than did digests of unmodified C5. After cleavage of oxidized C5 by gi
ngipain-R, the digest exhibited measurably greater neutrophil enzyme r
elease and chemotaxis of human polymorphonuclear leukocytes (PMNs) com
pared with the activities of unoxidized C5 digests. Gingipain-K genera
tes virtually no polarization or chemotactic activity of human PMNs fr
om C5, nor is enzyme release stimulated by these C5 digests. However,
when oxidized C5 was digested by gingipain-K, human PMNs were stimulat
ed for polarization, chemotaxis and enzyme release indicating that an
active fragment had been generated. Proteolysis of oxidized C5 evokes
greater neutrophil activation than does proteolysis of unoxidized prot
ein, a fact which supports the hypothesis that oxidation and proteolys
is may be coupled to enhance the destructive effects of the inflammato
ry process. These results, in which digests of both oxidized and unmod
ified complement component C5 were evaluated, support the general conc
ept that oxidation and proteolysis may participate cooperatively in am
plifying both the severity and duration of the inflammatory reaction.