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-glucopyranoside branches, has marked antitumor effects in syngeneic and autochtonous hosts. Clinically, LNT has proved effective with chemotherapeutic agents in patients with recurrent gastric and colorectal cancer. However, the mechanism that triggers subsequent immunologic reactions remains obscure. We hypothesized that LNT must first bind to the host cells. Accordingly, we analyzed LNT binding to host cells in healthy volunteers after incubating their cells under a variety of conditions as well as intravenously injecting LNT then subjecting them to flow cytometry and immunofluorescent staining using monoclonal antibody (anti-LNT mAb). LNT bound to monocytes and neutrophils, but not to lymphocytes in vitro. The most avid LNT binding was to monocytes. The percentage of LNT-bound monocytes after 60 min incubation at 4 degrees C was greater than 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 receptor (anti-CR1) mAb, and completely by anti-CR1 and anti-CR3 mAb together. The percentages of LNT-binding monocytes in the peripheral blood increased significantly 3 and 4 after 2 mg LNT-injection and returned to low levels 5 h later. However, no increase in LNT-binding neutrophils and lymphocytes was observed. We concluded that binding of LNT to human monocytes may initiate the influence of this compound on the immune system and differ between individuals. Its binding site may be similar to the C3b receptor.
Oka
M
M
Department of Surgery II, Yamaguchi University School of Medicine, Japan.
Hazama
S
S
Suzuki
M
M
Wang
F
F
Wadamori
K
K
Iizuka
N
N
Takeda
S
S
Akitomi
Y
Y
Ohba
Y
Y
Kajiwara
K
K
Suga
T
T
Suzuki
T
T
D000328:Adult; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007912:Lentinan / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D017463:Receptors, Complement 3b / Q000378:metabolism; D013696:Temperature
D017463:Receptors, Complement 3b; D007912:Lentinan