Open AccessTetanus Toxoid‐Pulsed Monocyte Vaccination for Augmentation of Collateral Vessel Growth
Author(s) -
Herold Joerg,
Francke Alexander,
Weinert Soenke,
Schmeisser Alexander,
Hebel Katrin,
Schraven Burkhart,
Roehl FriedichWilhelm,
Strasser Ruth H.,
BraunDullaeus Ruediger C.
Publication year - 2014
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.113.000611
Subject(s) - arteriogenesis , medicine , toxoid , transplantation , immunology , innate immune system , immune system , in vivo , hindlimb , ex vivo , acquired immune system , immunization , angiogenesis , biology , microbiology and biotechnology
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 <0.001), with no (0%) detectable functional impairment. ttMo injected into nonimmunized mice had no effect. The strong arteriogenic response of ttMo transplantation into immunized mice was prevented when mice had been depleted of T‐helper cells by CD 4‐antibody pretreatment ( PI =0.50±0.08; n=17; P <0.001), supporting the hypothesis that transplanted cells interact with recipient lymphocytes. 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.