Chemotactic activity of C5a des Arg: Evidence of a requirement for an anionic peptide ‘helper factor’ and inhibition by a cationic protein in serum from patients with systemic lupus erythematosus

Abstract

Sera from some patients with systemic lupus erythematosus (SLE) ∗ contain a uniquely specific, reversible inhibitor of complement (C5)-derived chemotactic activity for polymorphonuclear leukocytes. SLE serum, proven capable of significantly inhibiting C5-derived chemotactic activity in zymosan-treated serum (ZTS), was found incapable of inhibiting the chemotactic activity of the highly purified human anaphylatoxin, C5a (10–20 ng/ml). Similarly, SLE serum was found incapable of inhibiting the chemotactic activity generated in ZTS containing the carboxypeptidase inhibitor, epsilon amino-caproic acid (EACA). EACA protects C5a from the action of the anaphylatoxin inactivator in serum and thereby prevents conversion of C5a to a peptide (C5a des Arg) which is completely devoid of anaphylatoxin activity. Highly purified human C5a des Arg (40–160 μg/ml) was not chemotactic unless assayed in the presence of small amounts of normal human serum. The ‘helper factor’ in normal human serum which permits C5a des Arg to exhibit chemotactic activity was isolated and found to be an anionic polypeptide. The chemotactic activity of C5a des Arg plus normal serum was inhibited significantly by SLE serum. The inhibitor in SLE serum was isolated and determined to be a 69,000 mol. wt cationic protein. These data suggest strongly that the cationic inhibitor in SLE serum acts not on C5a but only on the ‘complex’ of C5a des Arg plus a specific peptide ‘helper factor’. This ‘complex’ accounts for a substantial proportion of the chemotactic activity in ZTS.