Enhancement by IgM rheumatoid factor of <i>in vitro</i> ingestion by macrophages and <i>in vivo</i> clearance of aggregated IgG or antigen‐antibody complexes

Abstract

Abstract Polyclonal as well as monoclonal IgM rheumatoid factors (RF) markedly enhanced both the attachment and ingestion of heat‐aggregated human IgG (HAG) by mouse alveolar macrophages, mouse peritoneal macrophages and human peripheral monocytes. This effect depended upon the integrity of the Fc fragment of the HAG as shown by the experiments performed with reduced and alkylated HAG. Marked differences in the stimulation index were observed between the five tested RF. When we compared the effect of complement (C) and/or RF on the total amounts of HAG cleared from the medium, i.e. the sum of the HAG associated with the cells and the digestion products released in the medium, the addition of C alone resulted in a 10‐fold increase, the addition of RF alone in a 20‐fold increase, and the addition of both RF and C in a 10‐fold increase. Apparently, the effect of RF was mainly on the binding of HAG to macrophages, whereas C mainly induced ingestion as indicated by the increased release of degradation products. Antigen‐antibody (AgAb) complexes were prepared with 125 I‐labeled human transferrin as antigen and mouse anti‐transferrin serum at various Ag/Ab ratios. Without RF, a significant uptake occurred up to a 3‐fold Ag excess. RF caused a 3‐fold increase of the uptake of complexes prepared at equivalence, but an 80‐fold increase of the uptake of the complexes prepared in 10‐fold Ag excess. Gradient ultracentrifugation of the AgAb complexes showed that the enhancement of the uptake due to RF was related to the increase of the sedimentation rate of the complexes. However, an excess of RF decreased its enhancing effect on endocytosis. One hour after the intraperitoneal injection of complexes in 10‐fold Ag excess, the radioactivity of the peritoneal cells was 14 times higher when the complexes were pre‐incubated with RF than with complexes not preincubated with RF. Similar complexes were also injected intravenously. The 13 S fraction which was visible on the ultracentrifugation profile in the absence of RF was eliminated very slowly, whereas the “heavy” fraction (&gt; 30 S) which appeared after addition of RF, was cleared from the plasma in 25 sec.