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2017 ; 101
(2
): e49-e56
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Underlying Mechanisms of Protection Involved in Immunocloak
#MMPMID27764033
Brasile L
; Henry N
; Stubenitsky B
Transplantation
2017[Feb]; 101
(2
): e49-e56
PMID27764033
show ga
BACKGROUND: We have previously reported on a novel organ-specific immunomodifying
therapy that provides protection from early allograft rejection in the absence of
systemic immunosuppressive drugs. This novel therapy is a nanobarrier membrane
called ImmunoCloak, consisting of a matrix of laminin, proteoglycans,
fibronectin, and collagens. The membrane "immunocloaks" the luminal surfaces
within the renal vasculature by covering the point of contact between donor
vascular endothelial cells and the recipient's immune cells, without adversely
affecting renal function. The resulting nonthrombogenic and nonimmunogenic apical
surface significantly delays the onset of rejection fivefold over untreated
controls. Currently, our focus is to elucidate the mechanisms of protection
provided by placement of the membrane. METHODS: The mechanisms underlying the
protective effect of the ImmunoCloak treatment was evaluated using human
peripheral blood mononuclear cells and by testing for antigen presentation by
cytokine/chemokine analysis using the Luminex platform, T cell allogeneic
responses were measured by flow cytometry, and diapedesis was assessed using
transwell plates. RESULTS: We now report that ImmunoCloak interrupts antigen
presentation thereby preventing early T cell activation and interferes with
diapedesis. There was significant inhibition in the synthesis of proinflammatory
cytokines with a concordant blockade of T cell-mediated responses. The placement
of the ImmunoCloak also significantly reduced leukocyte migration through the
endothelial cell layer by 93%. CONCLUSIONS: Eliminating the need for nephrotoxic
immunosuppressive drugs during the early posttransplant period could help to
ameliorate the severity of delayed graft function and could provide a path to
using more ischemically damaged renal allografts.
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