Response of human neutrophils to C5a: a role for the oligosaccharide moiety of human C5ades Arg-74 but not of C5a in biologic activity
Gerard, C.; Chenoweth, D.E.; Hugli, T.E.
Journal of Immunology 127(5): 1978-1982
1981
ISSN/ISBN: 0022-1767 PMID: 7299121 Document Number: 181244
HumanC5a [complement component 5a] anaphylatoxin and its des Arg-74-derivative (C5ades Arg-74) are glycopolypeptides with a complex oligosaccharide moiety linked to the side chain of an asparagine residue at position 64 in the polypeptide chain. To determine the role of this oligosaccharide moiety in the modulation of human C5a and C5ades Arg-74 biologic activities, native and deglycosylated human C5a, C5ades Arg-74 and its deglycosylated analog were prepared. These 4 human polypeptides and the naturally occurring nonglycosylated polypeptides porcine C5a and C5ades Arg-74 were evaluated for their ability to promote neutrophil chemotaxis, enhance lysosomal degranulation of these cells and interact with the human neutrophil C5a receptor. In all instances native and deglycosylated human C5a behaved identically. Deglycosylated human C5ades Arg-74 was .apprx. 10-fold more active than native C5ades Arg-74 as judged by bioassays. Deglycosylated C5ades Arg-74 displayed 10-fold enhancement of its ability to interact with the neutrophil C5a receptor compared with native C5ades Arg-74. Both porcine C5a and C5ades Arg-74 displayed a complete range of neutrophil-related biologic activities when evaluated with human cells, although these polypeptides are some 3- to 8-fold less active than their respective human analogs. The oligosaccharide moiety does not alter the biologic activities of human C5a. The oligosaccharide group appears to act as a significant negative modulator of the biologic activities of the less potent human C5ades Arg-744 derivative.