IN-VITRO AND IN-VIVO ANALYSIS OF HUMAN-LEUKOCYTE BINDING BY THE ANTITUMOR POLYSACCHARIDE, LENTINAN

Lentinan (LNT), a (1-->3)-beta-D-glucan with (1-->6)-beta-D-glucopyran oside branches, has marked antitumor effects in syngeneic and autochto nous hosts. Clinically, LNT has proved effective with chemotherapeutic agents in patients with recurrent gastric and colorectal cancer. Howe ver, the mechanism that triggers subsequent immunologic reactions rema ins obscure. We hypothesized that LNT must first bind to host cells. A ccordingly, we analyzed LNT binding to host cells in healthy volunteer s after incubating their cells under a variety of conditions as well a s intravenously injecting LNT then subjecting them to flow cytometry a nd immunofluorescent staining using monoclonal antibody (anti-LNT mAb) . LNT bound to monocytes and neutrophils, but not to lymphocytes in vi tro. The most avid LNT binding was to monocytes. The percentage of LNT -bound monocytes after 60 min incubation at 4 degrees C was greater th an that at 37 degrees C. The binding of LNT to monocytes was inhibited slightly by anti-iC3b receptor (anti-CR3) mAb, strongly by anti-C3b r eceptor (anti-CR1) mAb, and completely by anti-CR1 and anti-CR3 mAb to gether. The percentage of LNT-binding monocytes in the peripheral bloo d increased significantly 3 and 4 h after 2 mg LNT-injection and retur ned to low levels 5 h later. However, no increase in LNT-binding neutr ophils and lymphocytes was observed. We conclude that binding of LNT t o human monocytes may initiate the influence of this compound on the i mmune system and differ between individuals. Its binding site may be s imilar to the C3b receptor.