title: Tetanus toxoid-pulsed monocyte vaccination for augmentation of collateral vessel growth.
abstract: 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.
  
  
  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 CD4-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.
authors.affiliation: Internal Medicine/Cardiology, Angiology and Pneumology, Magdeburg University, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Herold
authors.forename: Alexander
authors.initials: A
authors.lastname: Francke
authors.forename: Soenke
authors.initials: S
authors.lastname: Weinert
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmeisser
authors.forename: Katrin
authors.initials: K
authors.lastname: Hebel
authors.forename: Burkhart
authors.initials: B
authors.lastname: Schraven
authors.forename: Friedich-Wilhelm
authors.initials: FW
authors.lastname: Roehl
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Strasser
authors.forename: Ruediger C
authors.initials: RC
authors.lastname: Braun-Dullaeus
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D003097:Collateral Circulation; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D006614:Hindlimb; D007113:Immunity, Innate; D007114:Immunization; D007511:Ischemia / Q000097:blood / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000637:transplantation*; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic; D020127:Recovery of Function; D012039:Regional Blood Flow; D013601:T-Lymphocytes / Q000276:immunology; D013745:Tetanus Toxoid / Q000008:administration & dosage* / Q000276:immunology; D013997:Time Factors
chemical_list: D016207:Cytokines; D013745:Tetanus Toxoid
keywords: arteriogenesis; cell transplantation; innate and adaptive immune system; monocyte; tetanus toxoid
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