C5a-Mediated Leukotriene B4-Amplified Neutrophil Chemotaxis is Essential in Tumor Immunotherapy Facilitated by Anti-Tumor Monoclonal Antibody and ß-Glucan
Daniel J. Allendorf, Jun Yan, Gordon D. Ross, Richard D. Hansen, Jarek T. Baran, Krishnaprasad Subbarao, Li Wang, and Bodduluri Haribabu
The Journal of Immunology, 2005, 174: 7050–7056.
Intravenous and orally administered ß-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 ß-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 ß-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 B4, because both C5a-mediated leukocyte recruitment into the peritoneal cavity and tumor regression were suppressed in leukotriene B4R-deficient (BLT-1-/-) mice.