title: Group B streptococci inactivate complement component C5a by enzymic cleavage at the C-terminus.
abstract: Incubation of recombinant human C5a (rC5a) with the 7360 strain of group B streptococci (GBS) destroyed the ability of rC5a to stimulate chemotaxis or adherence of purified human polymorphonuclear leucocytes (PMNs). Treatment of 125I-labelled rC5a with GBS 7360 correspondingly decreased rC5a binding to human PMNs. This also resulted in an approx. 600 Da decrease in the molecular mass of rC5a as determined by SDS/PAGE. Incubation of rC5a with the GBS strain GW, which only minimally altered the ability of rC5a to activate human PMNs, did not affect rC5a binding to PMNs and did not alter the molecular mass of rC5a on SDS/PAGE. Plasma-desorption m.s. of rC5a inactivated by GBS 7360 showed that the GBS cleaved the rC5a between histidine-67 and lysine-68 near the C-terminus of rC5a. This mechanism of inactivation of C5a by proteolytic cleavage at the C-terminus of C5a is consistent with the known critical role of the C-terminus in C5a activation of human PMNs. This C5a-cleaving proteinase activity may contribute to the pathophysiology of GBS infections.
authors.affiliation: Department of Pediatrics, University of Utah School of Medicine, Salt Lake City 84132.
authors.forename: J F
authors.initials: JF
authors.lastname: Bohnsack
authors.forename: K W
authors.initials: KW
authors.lastname: Mollison
authors.forename: A M
authors.initials: AM
authors.lastname: Buko
authors.forename: J C
authors.initials: JC
authors.lastname: Ashworth
authors.forename: H R
authors.initials: HR
authors.lastname: Hill
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002634:Chemotaxis, Leukocyte; D015936:Complement C5a / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000494:pharmacology; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009504:Neutrophils / Q000502:physiology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D013292:Streptococcus agalactiae / Q000201:enzymology*; D013379:Substrate Specificity
chemical_list: D011994:Recombinant Proteins; D015936:Complement C5a; D010450:Endopeptidases