The recommendations in this Guideline reflect the currently available evidence. New clinical research data will necessitate a revision and update in the future.

Although interactions of proteins with glycosaminoglycans (GAGs), such as heparin and heparan sulphate, are of great biological importance, structural requirements for protein‐GAG binding have not been well‐characterised. Ionic interactions are important in promoting protein‐GAG binding. Polyelectrolyte theory suggests that much of the free energy of binding comes from entropically favourable release of cations from GAG chains. Despite their identical charges, arginine residues bind more tightly to GAGs than lysine residues. The spacing of these residues may determine protein‐GAG affinity and specificity. Consensus sequences such as XBBBXXBX, XBBXBX and a critical 20 Å spacing of basic residues are found in some protein sites that bind GAG. A new consensus sequence TXXBXXTBXXXTBB is described, where turns bring basic interacting amino acid residues into proximity. Clearly, protein‐GAG interactions play a prominent role in cell‐cell interaction and cell growth. Pathogens including virus particles might target GAG‐binding sites in envelope proteins leading to infection. BioEssays 20:156–167, 1998. © 1998 John Wiley & Sons, Inc.

An inhibitory activity for an erythrocyte intermediate bearing the properdin (P)-stabilized amplification C3 convertase, PC3bBb, was recognized in whole normal human serum and separated from C3b inactivator by its distinct physicochemical and functional characteristics. The inhibitory activity was found to reside in a protein that was purified to homogeneity and elicited a monospecific antibody in a rabbit. This protein was identified as P11H and found to have a serum concentration of 516 + 89 yg/ml (mean ±1 SD The complement system, which is comprised of at least 18 plasma proteins, consists of four functional divisions: two pathways for activation, the classical and alternative (properdin); a single amplification mechanism that is recruited by each activating pathway; and a final common effector pathway to which the activating and amplifying sequences are directed and from which are derived the biologic activities of complement (1, 2). Activation of the classical pathway by antigenantibody complexes containing immunoglobulin of the appropriate class involves conversion of C1 from its precursor form to an active state, C1 (3), with subsequent cleavage of C4 (4) and C2 to form C4b2a (5), the classical C3 convertase that initiates cleavage of C3. Activation of the alternative pathway occurs with certain microbial polysaccharides that interact with B, D, C3, and other proteins to achieve initial CS cleavage (6).The major cleavage fragment of CS, C3b, generated by either activating sequence, then interacts with B and D (7) to form the amplification convertase, C3bBb (8, 9).Abbreviations: P, activated properdin; PC3bBb, properdin-stabilized amplification CS convertase; C3NeF, CS nephritic factor; CMbINA, C3b inactivator; DGVB++, half-isotonic Veronal-buffered saline, 0.1% gelatin, 0.5 mM magnesium, 0.15 mM calcium, and 2.5% dextrose; DGVB-EDTA, half-isotonic Veronal-buffered saline, 0.1% gelatin, 0.01 M EDTA, and 2.5% dextrose; C-EDTA, rat serum diluted 1:20 in Veronal-buffered saline, 0.1% gelatin and 0.04 M EDTA. * To whom reprint requests should be addressed.In the amplification step, C3b serves as a receptor for B (9) in a magnesium-dependent binding reaction'that partially reveals the proteolytic site in B for C3 (10). D, a protease of the serine esterase class (11), cleaves bound B to release the Ba fragment and to uncover fully the CS-cleaving site on Bb which remains bound. The C3bBb complex is labile because of irreversible decay-dissociation of Bb, but can be regenerated on the residual C3b by the uptake of additional B and its cleavage by D (9). Activated properdin (P) binds to C3b (12-14), and CS nephritic factor (C3NeF), a serum protein found in some patients with hypocomplementemic membranoproliferative glomerulonephritis, binds to C3bBb (15); both proteins stabilize the convertase and increase its half-life by as much as 10-fold, thereby profoundly augmenting amplification of CS cleavage (12,16).Control of the amplification pathway is regulated by the inherent lability of the C3bBb convertase...

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