C5a-Mediated Leukotriene B4-Amplified Neutrophil Chemotaxis Is Essential in Tumor Immunotherapy Facilitated by Anti-Tumor Monoclonal Antibody and Beta-Glucan
The Journal of Immunology, 2005, 174: 7050–7056.
Daniel J. Allendorf,*† Jun Yan,2*† Gordon D. Ross,3*‡† Richard D. Hansen,* Jarek T. Baran,4* Krishnaprasad Subbarao,5* Li Wang,* and Bodduluri Haribabu*†
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 B4, because both C5a-mediated leukocyte recruitment into the peritoneal cavity and tumor regression were suppressed in leukotriene B4R-deficient (BLT-1-/-) mice.
Published at wellmune.com on 19 June 2005