C5a-mediated leukotriene B4-amplified neutrophil chemotaxis is essential in tumor immunotherapy facilitated by anti-tumor monoclonal antibody and beta-glucan.
Intravenous and orally administered beta-glucans promote tumor regression and survival by priming granulocyte and macrophage C receptor 3 (CR3, iC3bR and CD11b/CD18) to trigger the cytotoxicity of tumor cells opsonized with iC3b via anti-tumor Abs. Despite evidence for priming of macrophage CR3 by oral beta-glucan in vivo, the current study in C57BL/6 and BALB/c mice showed that granulocytes were the essential killer cells in mAb- and oral beta-glucan-mediated tumor regression, because responses were absent in granulocyte-depleted mice. Among granulocytes, neutrophils were the major effector cells, because tumor regression did not occur when C5a-dependent chemotaxis was blocked with a C5aR antagonist, whereas tumor regression was normal in C3aR(-/-) mice. Neutrophil recruitment by C5a in vivo required amplification via leukotriene B(4), because both C5a-mediated leukocyte recruitment into the peritoneal cavity and tumor regression were suppressed in leukotriene B(4)R-deficient (BLT-1(-/-)) mice.
Allendorf
Daniel J
DJ
Tumor Immunobiology Program of the James Graham Brown Cancer Center, University of Louisville School of Medicine, KY 40202, USA.
Yan
Jun
J
Ross
Gordon D
GD
Hansen
Richard D
RD
Baran
Jarek T
JT
Subbarao
Krishnaprasad
K
Wang
Li
L
Haribabu
Bodduluri
B
D000284:Administration, Oral; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D015926:Complement C3a / Q000502:physiology; D015936:Complement C5a / Q000502:physiology*; D006098:Granulocytes / Q000166:cytology / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D007975:Leukotriene B4 / Q000502:physiology*; D008223:Lymphoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology*; D018102:Receptors, Leukotriene B4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D047071:beta-Glucans / Q000008:administration & dosage / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D018102:Receptors, Leukotriene B4; D047071:beta-Glucans; D007975:Leukotriene B4; D015926:Complement C3a; D015936:Complement C5a