Evidence against a role for neutrophils in the clearance of small immune complexes

The activation of human neutrophils (PMN) by immune complexes (IC) consisting of tetanus toxoid and the corresponding human antibodies was studied by varying IC properties like size, antigen: antibody ratio, Fc density, etc. While Ag: ab ratio seemed to have some importance, especially when complement activation was allowed, size appeared to be the decisive factor. Surprisingly, good stimulation of PMN was obtained only with very large IC and no plateau was reached with increasing size. PMN activation even by these very large complexes was inhibited in the presence of physiological IgG concentrations, but only if complement was omitted. Generation of IC in the presence of serum, on the other hand, prevented the formation of IC sufficiently large for PMN activation. Finally, in an IC clearance experiment in mice using 125I-labelled human serum albumin and mouse antibody, no radioactivity was found associated with blood PMN in spite of a rapid clearance. It is concluded that PMN are probably not involved in the physiological clearance of IC if these are considerably smaller than opsonized microorganisms.