An Alternative Hypothesis for the ‘Properdin System’

Experimental results have been obtained which support a hypothesis that the chief characteristics of the “properdin system” may be explained in terms of a classical antigen-antibody system involving complement (C), provided that antibody (Ab) is present in small amounts. Specifically, the hypothesis states that: 1. The zymosan-properdin (Z·P) complex represents varying proportions of Z·Ab·C’14, Z·Ab·C’142 and Z·Ab·C142 in a decayed state (the amounts of the latter will be dependent upon time and temperature involved in preparation and purification). 2. The purported selective inactivation of C’3 by zymosan reacting with whole serum was misconstrued from expression of residual C in percentage rather than in units. Since there are 15 to 20 times as many C\4 units as G’3 units in whole serum, an equivalent loss of both C’14 and C’3 units appears to be more significant for C3 when results are expressed as percentage loss. The presence of Ab in normal serum which reacts with zymosan has been implicated by agglutination, immune-adherence, and complement-fixation. Quantitative uptake of protein nitrogen (N) by zymosan reacting with human sera demonstrated absorbed protein ranging from 1 or 2 /¿g to 30 or 40 μg N per ml of serum. In quantitative measurements of fixation of G’14 and of C’3 (modelled after the procedures of Levine and Mayer) significant amounts of both C’1 > 4 (about 500 units) and C’3 (about 150 units) were fixed by zymosan mixed with normal guinea pig serum. Essentially similar ratios of C’ components were fixed in assays with Diþlococcus þneumoniae and bovine serum albumin mixed with small amounts of their respective antibody. These results suggested that certain unique aspects of the properdin system could be explained as due to the small amount of Ab available in normal serum. Another presumably unique aspect of the properdin system involves: a) the requirement for Mg++ both in the formation of Z · P and in the reaction of Z · P with C’3; and b) the requirement for concentration of Mg++ which are about 10 times the optimal for lysis in the classic hemolytic system. Independent studies 276 Nelson, Jr. by Woodworth demonstrated that optimal reactivity of human C in immune-adherence assays requires .01 M Mg+> and .001 M Ca++, both of which are strikingly higher than needed in immune hemolysis with guinea pig serum. Also, evidence has been obtained which shows that the complex Z·Ab·C’1 > 4 > 2 may be formed and that this complex reacts with C3 in the absence of either Ca++ or Mg++. On the basis of the work of Levine and Mayer it would be expected that decay of this intermediate would require Mg++ in order to fix new C’2 before reacting with C’3. In the presence of a chelating agent and at O°C, purified properdin, obtained from Dr. L. Pilíemer, agglutinated zymosan. Under the same conditions, initial measurements of N uptake by zymosan indicate that about 0.25 μg protein N are contributed by amounts stated to be equivalent