DUAL PERTUSSIS-TOXIN-SENSITIVE PATHWAY OF ZYMOSAN-INDUCED ACTIVATION GUINEA-PIG MACROPHAGES - AN ANTI-CR3 ANTIBODY-INHIBITABLE STIMULATION OF PHAGOCYTOSIS AND RESISTANT STIMULATION OF O-2(-) PRODUCTION AND ARACHIDONATE RELEASE

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; generation was unchanged. The Fab' fragment of anti-Z-1, a monoclonal antibody specific for the a 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.