Analysis of the interactions between properdin, the third component of complement (C3), and its physiological activation products.
The interactions of properdin with both surface-bound and fluid-phase C3 (the third component of complement) and its activation products have been investigated by using a purified preparation of the 'native' form. At physiological ionic strength, a weak interaction with cell-bound C3b (the larger activation fragment of C3) could be demonstrated. In the presence of Factor B this interaction was enhanced, and further enhancement was seen when C3bBb sites were formed on the erythrocytes. The avidities of properdin for cell-bound iC3b (the initial product of Factors I and H action on C3b) and C3b were compared at low ionic strength, with that measured for iC3b being less than that for C3b. In contrast, the affinities of properdin for fluid-phase C3b, iC3b and C3c (the larger product of Factors I and H or CR1 (the C3b receptor) action on iC3b) were all very similar, and apparently much weaker than that for cell-bound C3b. No interaction with either native C3 or, more surprisingly, C3i (haemolytically inactive C3) could be detected. Properdin also inhibited Factor I binding to, and action upon, cell-bound C3b, but did not inhibit Factor I action on fluid-phase C3b. These data permit a more detailed description of the roles of properdin in the alternative pathway of complement activation, emphasizing its importance in concentrating activation at the activating surface.
Farries
T C
TC
Mechanisms in Tumour Immunity Unit, MRC Centre, Cambridge, U.K.
Lachmann
P J
PJ
Harrison
R A
RA
D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism*; D050577:Complement C3-C5 Convertases / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism; D011415:Complement Factor B / Q000378:metabolism; D003170:Complement Pathway, Alternative; D004912:Erythrocytes / Q000276:immunology*; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D008954:Models, Biological; D009994:Osmolar Concentration; D011414:Properdin / Q000378:metabolism*; D011485:Protein Binding
D003176:Complement C3; D046911:Macromolecular Substances; D011414:Properdin; D003179:Complement C3b; D005340:Fibrinogen; D050577:Complement C3-C5 Convertases; D011415:Complement Factor B