LEUKOCYTE ACTIVATION BY ANTI-LACTOFERRIN ANTIBODIES BOUND TO VASCULARENDOTHELIUM

Human polymorphonuclear neutrophil leucocytes (PMNL) prestimulated wit h the formylated tripeptide f-Met-Leu-Phe (fMLP) were activated to an immediate chemiluminescence (CL) response by polyclonal rabbit antibod ies against human lactoferrin (Lf). This activation, indicat ing the f ormation of reactive oxygen species, was induced by intact IgG antibod ies but could not be brought about by F(ab')(2) fragments. Human Lf wa s also shown to adhere to the surface of cultured bovine aorta endothe lial cells (BEG). When Lf-coated BEC grown on microcarrier beads were reacted with anti-Lf antibodies, an immediate CL response was achieved also with non-primed PMNL. Here, too, the reaction required intact Ig G antibodies. Also, patient sera containing anti-Lf autoantibodies of IgG class were shown to activate fMLP-treated PMNL. The same effect wa s obtained (in a dose-dependent manner) with the gammaglobulin fractio n from anti-Lf-positive patient serum. Further, anti-Lf-antibody-posit ive patient sera incubated with Lf-coated BEC beads were also able to activate non-stimulated PMNL to a chemiluminescence response. The resu lts are discussed in relation to possible mechanisms of cell/tissue da mage induced by anti-neutrophil cytoplasmic antibodies (ANCA).