A Specific Inhibitor of Complement (C5)-Derived Chemotactic Activity in Serum from Patients with Systemic Lupus Erythematosus

Abstract

A B S T R A C T In the course of examining polymorphonuclear leukocyte (PMN) chemotaxis in patients w7ith systemic lupus erythematosus (SLE), we have found a previously undescribed serum inhibitor of complement (C5)-derived chemotactic activity. Serum from a 25-yr-old Black f'emale with untreated SLE, when activated with zymosan, failed completely to attract either her own or normal PMN. Incubation of normal PMN with the patient's serum did not aff'ect their subsequent random motility or chemotactic response toward normal zymosan-treated serum (ZTS). The patient's serum, however, did inhibit the chemotactic activity of normal ZTS and of column-purified C5-derived peptide(s), but had no effect on the chemotactic activity of either the synthetic peptide, N-formylmethionyl leucyl-phenylalanine or a filtrate prepared from a culture of Escherichia coli (bacterial chemotactic factor). The inhibitory activity in the patient's serum resisted heating at 56°C for 30 min and could be separated f'rom C5-derived chemotactic activity in the patient's ZTS (or normal ZTS that had been incubated with the patient's serum) by chromatography on Sephadex G-75. Despite its effect on C5-derived chemotactic activitv, the patient's serum did not influence two other C5-derived biologic activities: PMN lysosomal enzyme-releasing activity and PMN-aggregating activity. Chromatography of the patient's serum (65% ammonium sulfate pellet) on Sephadex G-200 yielded three distinct peaks of inhibitory activity. Two were This work was presented in part at the Eastern Section

Serum Inhibitor of C5 Fragment-Mediated Polymorphonuclear Leukocyte Chemotaxis Associated with Chronic Hemodialysis

“…In this case, the factor-directed inhibitors could protect the host from adverse effects of excessive CS-fragment generation. Consistent with this hypothesis is the finding of a similar inhibitor in systemic lupus erythematosis (31), another condition also associated with chronic complement activation and therefore C5 fragment generation.…”

“…The inhibitor consists of a major 4S heatstable substance directed at CD chemotactic factor. This inhibitor resembles the factor-directed inhibitor found in patients with systemic lupus erythematosis (31). It is proposed that this inhibitor may be released from granulocytes during HD or be a host response to control C5a generation associated with HD.…”

Increased endothelial cell adherence, aggregation, and superoxide generation by neutrophils incubated in systemic lupus erythematosus and felty's syndrome sera

“…Serum factor(s) which interfere with PMN phagocytosis have been reported (12). The chemotactic function of PMN from SLE patients has been shown to be reduced (10,l I), and chemotaxis inhibition has been detected in some SLE sera (13,14).…”

“…Sera were obtained from 31 patients with SLE ( I male, 30 females; mean age 34), 20 patients with Felty's syndrome (5 male, 15 females; mean age 54), 24 patients with RA (2 males, 22 females; mean age 54), and 34 normal persons (12 male, 22 females; mean age 32). All SLE patients fulfilled the American Rheumatism Association criteria for SLE (14). SLE patients were divided into groups of 19 clinically active and 12 inactive patients.…”

“…In view of the important role of polymorphonuclear neutrophils (PMN) in the pathogenesis of well established immune complex diseases such as experimental serum sickness (8), it was desirable to investigate possible abnormalities of PMN function in SLE. Impaired phagocytic activity and chemotaxis of PMN from SLE patients (9-11) and serum and/or plasma inhibitors of these functions (12)(13)(14) have been demonstrated. These ac-tions may contribute t o the high incidence of infection seen in SLE (I 5).…”