Chemotactic activity of C5ades 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

Sera from some patients with systemic lupus erythematosus (SLE)¹ 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.