Macrophage-Fc-receptor affinity: role in cellular mediation of antibody initiated glomerulonephritis.
The role of immunoglobulin (Ig) Fc-macrophage cell surface receptor affinity (macrophage Fc-affinity) in determining the mediation systems responsible for immune glomerular injury has been studied. Glomerular injury was initiated in rabbits by the passive administration of immunoglobulin preparations directed against a "planted" glomerular antigen. The mediation systems inducing injury initiated by antibody pools of high and low macrophage Fc-affinity were compared. In this model of glomerulonephritis macrophage Fc-affinity was the only variable. IgFc-macrophage affinity was quantitated in fluid-phase and solid-phase assay systems (high affinity pool KA = 7.05 +/- 1.11 x 10(5) L/M; low affinity pool KA = 0.79 +/- 0.13 x 10(5) L/M). Comparative antibody binding studies demonstrated that renal injury occurred with high affinity antibody at kidney-fixed-antibody (KFA) binding levels significantly below the KFA levels required for glomerular injury with administration of low affinity antibody [KFA's: 25.1 +/- 2.1 micrograms antibody globulin/g kidney cortex (micrograms/g) and 60.5 +/- 2.4 micrograms/g, respectively, P less than 0.01]. Furthermore, antibody with high macrophage Fc-receptor affinity induced a macrophage-mediated, complement-independent glomerular injury while antibody with low macrophage Fc-receptor affinity induced renal injury via complement and neutrophil dependent mechanisms. IgFc-receptor affinity determined the degree of macrophage recruitment into glomeruli via immune adherence mechanisms, and therefore is an important determinant of which inflammatory mediator system is ultimately responsible for antibody-initiated glomerular injury.
Boyce
N W
NW
Monash University Department of Medicine, Prince Henry's Hospital, Melbourne, Australia.
Holdsworth
S R
SR
D000818:Animals; D000915:Antibody Affinity / Q000276:immunology; D005921:Glomerulonephritis / Q000276:immunology*; D007678:Kidney Glomerulus / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D011817:Rabbits; D011961:Receptors, Fc / Q000276:immunology*
D011961:Receptors, Fc