IMMUNIZATION WITH MENINGOCOCCAL MEMBRANE-BOUND LIPOOLIGOSACCHARIDE ACCELERATES GRANULOCYTE RECOVERY ENHANCES LYMPHOCYTE-PROLIFERATION IN MYELOSUPPRESSED MICE

Protective effects of detergent-treated outer membrane vesicles (D-OMV s) prepared from the parent group B M986 strain and the nonencapsulate d M986-NCV mutant in myelosuppressed mice were investigated in models of experimental septic shock. The effects of D-OMVs on expansion of th e myeloid compartment, on spleen cell proliferation to mitogen stimula tion, and on cytokines induced during this period were investigated. O n 3 consecutive days, mice were injected with 1 mu g/kg of lipooligosa ccharide (LOS) or lipopolysaccharide, or 75 mu g/kg D-OMV followed by a single dose of cyclophosphamide (200 mg/kg) 24 h later, Eight weeks after the last injection, animals were challenged with a combination o f galactosamine (400 mg/kg) and live Neisseria meningitidis. More than 90% of control mice died within 24 h when challenged with 10(5) CFU o f bacteria. Mice immunized with LOS or D-OMV were rendered neutropenic but were protected against bacterial challenge of at least 10(7) CFU. At different time intervals, peripheral blood samples were obtained t o characterize changes in circulating blood cells. The rise in absolut e granulocyte numbers occurred 24 h earlier with peak cell counts abou t 3 times higher than those seen in the placebo groups, Peripheral blo od cells from D-OMV-treated animals expressed about twofold more Gr-1 antigen (myeloid surface cell marker) than placebo-treated controls. T he proliferative responses to both B and T cells were reduced in all t reatment groups due to the effects of cyclophosphamide. D-OMV treatmen t afforded the greatest protection for mitogen-activated lymphocytes f rom the lethal effects of cyclophosphamide and also enhanced T and B c ell proliferation. Low IL-1 beta levels and increases in serum IL-6 we re detected in all treatment groups. In contrast, significant IFN-gamm a and IL-3 levels were only detected in D-OMV-treated groups. These re sults indicate that D-OMVs, which have reduced toxicity, have prophyla ctic potential in inducing specific cytokines that accelerate granuloc yte recovery following cytoreductive therapy by promoting both prolife ration and maturation of myeloid precursors as well as augmenting the immune system.