Non-specific binding by macrophages: existence of different adhesive mechanisms and modulation by metabolic inhibitors

Abstract

Rat peritoneal cells were made to bind test particles of five different species: immunoglobulin-coated sheep red cells (IGSRC), glutaraldehyde-treated sheep red cells (GSRC), leishmania, latex beads and tumour cells. The dependence of binding on various physicochemical parameters was studied: the binding of latex or leishmania resisted cold (4 degrees), azide, cytochalasin B, ethyleneglycol and dimethylsulphoxide (DMSO). The binding of IGSRC resisted cold and azide, but it was inhibited by cytochalasin B, ethyleneglycol and DMSO. The binding of GSRC was inhibited by cold, azide and ethyleneglycol, but not by cytochalasin B and DMSO. The binding of tumour cells was inhibited by azide, cytochalasin B, ethyleneglycol and DMSO. An attempt was made to saturate selectively some adhesive sites of macrophage membranes: glutaraldehyde-treated bovine albumin (GBSA) inhibited the ingestion of latex and GSRC, not leishmania and IGSRC, whereas a crude leishmania extract (CLE) inhibited the ingestion of all tested particles except latex. Antigen-antibody complexes inhibited the ingestion of IGSRC and leishmania, not latex and GSRC. Rat macrophages were made to bind radio-iodinated GBSA (GIBSA). The uptake of glutaraldehyde-treated albumin was proportional to the amount of substrate the cells were incubated with over a wide concentration range. This uptake was not a result of endocytosis, and it was far more efficient than that of peroxidase. Macrophage-particle interaction was studied with electron microscopy. The binding of IGSRC and leishmania to macrophages involved large areas where the interacting membranes were separated by a low density gap of constant width. The interaction of GSRC and latex with macrophages was much more patchy and irregular. Further, no redistribution of the macrophage surface polysaccharides seemed associated with the binding of GSRC. It was concluded that several different mechanisms and different membrane adhesive structures are involved in non-specific recognition by macrophages. Further, non-specific binding sometimes requires an active cell participation. Several testable hypotheses are described, which suggest further experiments in order to obtain a fuller insight into the mechanism of rosette formation.