Dual pertussis toxin-sensitive pathway of zymosan-induced activation in guinea pig macrophages: An anti-CR3 antibody-inhibitable stimulation of phagocytosis and -resistant stimulation of O2− production and arachidonate release

Abstract Complement receptor type 3 (CR3)-mediated cellular responses in guinea pig macrophages were investigated by using zymosan and serum-opsonized zymosan (SOZ) as the multivalent ligand for CR3. The ingestion of zymosan and SOZ was accompanied by O 2 − generation and arachidonate release. These responses were suppressed by prior exposure of macrophages to pertussis toxin (PT). Opsonization of zymosan gave rise to more than 6-fold activation of the ingestion, whereas the magnitude of either arachinonate release or O 2 − generation was unchanged. The Fab' fragment of anti-Z-1, a monoclonal antibody specific for the α chain of guinea pig CR3, inhibited the ingestion of zymosan by 60% without affecting zymosan-induced arachidonate release and O 2 − generation. These data suggested that there might be at least two functionally distinct binding sites for zymosan. O 2 − generation and arachidonate release might be regulated through one site and phagocytosis another. Both sites should be coupled to PT-sensitive GTP binding protein.