Leucocyte activation by anti-lactoferrin antibodies bound to vascular endothelium

Abstract

SUMMARY Human polymorphonuclear neutrophil leucocytes (PMNL) prestimulated with the formylated tripeptide f-Met-Leu-Phe (fMLP) were activated to an immediate chemiluminescence (CL) response by polyclonal rabbit antibodies against human lactoferrin (Lf). This activation, indicating the formation of reactive oxygen species, was induced by intact IgG antibodies but could not be brought about by F(ab')2 fragments. Human Lf was also shown to adhere to the surface of cultured bovine aorta endothelial cells (BEC). 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 IgG antibodies. Also, patient sera containing anti-Lf autoantibodies of IgG class were shown to activate fMLP-treated PMNL. The same effect was obtained (in a dose-dependent manner) with the gammaglobulin fraction from anti-Lf-positive patient serum. Further, anti-Lf-antibody-positive patient sera incubated with Lf-coated BEC beads were also able to activate non-stimulated PMNL to a chemiluminescence response. The results are discussed in relation to possible mechanisms of cell/tissue damage induced by anti-neutrophil cytoplasmic antibodies (ANCA).