Tetanus toxoid-pulsed monocyte vaccination for augmentation of collateral vessel growth

Autor: Joerg Herold, Alexander Francke, Soenke Weinert, Burkhart Schraven, Ruediger C. Braun-Dullaeus, Alexander Schmeisser, Katrin Hebel, Friedich‐Wilhelm Roehl, Ruth H. Strasser
Rok vydání: 2014
Předmět:
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
ISSN: 2047-9980
Popis: Background The pathogenesis of collateral growth (arteriogenesis) has been linked to both the innate and adaptive immune systems. While therapeutic approaches for the augmentation of arteriogenesis have focused on innate immunity, exploiting both innate and adaptive immune responses has not been examined. We hypothesized that tetanus toxoid (tt) immunization of mice followed by transplantation of monocytes (Mo) exposed ex vivo to tt augments arteriogenesis after ligation of the hind limb. Methods and Results Mo were generated from nonimmunized BALB /c mice, exposed ex vivo to tt for 24 hours and intravenously injected (ttMo, 2.5×10 6 ) into the tail veins of tt‐immunized syngeneic mice whose hind limbs had been ligated 24 hours prior to transplantation. Laser Doppler perfusion imaging was applied, and a perfusion index ( PI ) was calculated (ratio ligated/unligated). Twenty‐one days after ligation, the arteriogenesis of untreated BALB /c mice was limited ( PI =0.49±0.09). Hind limb function was impaired in 80% of animals. Injection of non‐engineered Mo insignificantly increased the PI to 0.56±0.07. However, ttMo transplantation resulted in a strong increase of the PI to 0.82±0.08 (n=7; P CD 4‐antibody pretreatment ( PI =0.50±0.08; n=17; P Conclusions Transplantation of ttMo into pre‐immunized mice strongly promotes arteriogenesis. This therapeutic approach is feasible and highly attractive for the alleviation of morbidity associated with vascular occlusive disease.
Databáze: OpenAIRE