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.
Mechanisms in Tumour Immunity Unit, MRC Centre, Cambridge, U.K.
T C
TC
Farries
P J
PJ
Lachmann
R A
RA
Harrison
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