Soluble beta-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells

被引:324
作者
Vetvicka, V
Thornton, BP
Ross, GD
机构
[1] Div. Exp. Immunol. Immunopathology, Department of Pathology, University of Louisville, Louisville
关键词
immunotherapy; neoplasms; integrins; monoclonal antibodies; biological response modifiers;
D O I
10.1172/JCI118777
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
When phagocyte CR3 binds to iC3b on bacteria or yeast, phagocytosis and degranulation are triggered because of simultaneous recognition of iC3b via a CD11b I-domain binding site and specific microbial polysaccharides via a lectin site located COOH-terminal to the I-domain, By contrast, when phagocyte or natural killer (NK) eel CR3 adheres to iC3b on erythrocytes or tumor cells that lack CR3-binding membrane polysaccharides, neither lysis nor cytotoxicity are stimulated, This investigation showed that soluble CR3-specific polysaccharides such as beta-glucan induced a primed state of CR3 that could trigger killing of iC3b-target cells that were otherwise resistant to cytotoxicity, Anti-CR3 added before sugars prevented priming, whereas anti-CR3 added after sugars blocked primed CR3 attachment to iC3b-targets. Polysaccharide priming required tyrosine kinase(s) and a magnesium-dependent conformational change of the I-domain that exposed the CBRM1/5 activation epitope. Unlike LPS or cytokines, polysaccharides did not up-regulate neutrophil CR3 expression nor expose the mAb 24 reporter epitope representing the high affinity ICAM-1-binding state, The current data apparently explain the mechanism of tumoricidal beta-glucans used for immunotherapy, These polysaccharides function through binding to phagocyte or NK cell CR3, priming the receptor for cytotoxicity of neoplastic tissues that are frequently targeted with iC3b and sparing normal tissues that lack iC3b.
引用
收藏
页码:50 / 61
页数:12
相关论文
共 88 条
  • [41] MORIKAWA K, 1985, CANCER RES, V45, P1496
  • [42] CR3 (CD11B/CD18) EXPRESSED BY CYTOTOXIC T-CELLS AND NATURAL-KILLER-CELLS IS UP-REGULATED IN A MANNER SIMILAR TO NEUTROPHIL CR3 FOLLOWING STIMULATION WITH VARIOUS ACTIVATING AGENTS
    MUTO, S
    VETVICKA, V
    ROSS, GD
    [J]. JOURNAL OF CLINICAL IMMUNOLOGY, 1993, 13 (03) : 175 - 184
  • [43] NEUTROPHIL AND MONOCYTE CELL-SURFACE P150,95 HAS IC3B-RECEPTOR (CR4) ACTIVITY RESEMBLING CR3
    MYONES, BL
    DALZELL, JG
    HOGG, N
    ROSS, GD
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1988, 82 (02) : 640 - 651
  • [44] REGULATION OF STIMULATED INTEGRIN SURFACE EXPRESSION IN HUMAN NEUTROPHILS BY TYROSINE PHOSPHORYLATION
    NACCACHE, PH
    JEAN, N
    LIAO, NW
    BATOR, JM
    MCCOLL, SR
    KUBES, P
    [J]. BLOOD, 1994, 84 (02) : 616 - 624
  • [45] NAUTS HC, 1946, CANCER RES, V6, P205
  • [46] NEUMAN E, 1990, J IMMUNOL, V145, P3325
  • [47] NICULESCU F, 1992, AM J PATHOL, V140, P1039
  • [48] IMMUNOLOGICAL ANALYSIS AND CLINICAL EFFECTS OF INTRAABDOMINAL AND INTRAPLEURAL INJECTION OF LENTINAN FOR MALIGNANT ASCITES AND PLEURAL EFFUSION
    OKA, M
    YOSHINO, S
    HAZAMA, S
    SHIMODA, K
    SUZUKI, T
    [J]. BIOTHERAPY, 1992, 5 (02) : 107 - 112
  • [49] OREAR LD, 1994, CURRENT PROTOCOLS IM
  • [50] ANTIBODIES THAT ACTIVATE BETA-2 INTEGRINS CAN GENERATE DIFFERENT-LIGAND BINDING STATES
    ORTLEPP, S
    STEPHENS, PE
    HOGG, N
    FIGDOR, CG
    ROBINSON, MK
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1995, 25 (03) : 637 - 643