Should Complement Activation Be a Target for Therapy in Renal Transplantation?

Sheerin, Neil

doi:10.1681/asn.2008101064

Cited by 1 publication

(1 citation statement)

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“…6 Accumulating experimental and clinical evidence has demonstrated that the inhibition of complement activation can be a promising target for therapeutic intervention in organ transplantation. 50 To date, numerous therapeutic agents, such as monoclonal antibodies, small molecules, and small interfering RNA (siRNA) agents, have been developed to block complement cascade activation. The administration of soluble complement receptor-1 antagonist (sCR1), which inactivates the C3 and C5 convertases, results in reduced neutrophil migration into grafts and reduced posttransplantation reperfusion edema in a swine lung allotransplantation model.…”

Section: The Complement Cascadementioning

confidence: 99%

The innate immune response to allotransplants: mechanisms and therapeutic potentials

et al. 2019

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Surgical trauma and ischemia reperfusion injury (IRI) are unavoidable aspects of any solid organ transplant procedure. They trigger a multifactorial antigen-independent inflammatory process that profoundly affects both the early and long-term outcomes of the transplanted organ. The injury associated with donor organ procurement, storage, and engraftment triggers innate immune activation that inevitably results in cell death, which may occur in many different forms. Dying cells in donor grafts release damageassociated molecular patterns (DAMPs), which alert recipient innate cells, including macrophages and dendritic cells (DCs), through the activation of the complement cascade and toll-like receptors (TLRs). The long-term effect of inflammation on innate immune cells is associated with changes in cellular metabolism that skew the cells towards aerobic glycolysis, resulting in innate immune cell activation and inflammatory cytokine production. The different roles of proinflammatory cytokines in innate immune activation have been described, and these cytokines also stimulate optimal T-cell expansion during allograft rejection. Therefore, early innate immune events after organ transplantation determine the fate of the adaptive immune response. In this review, we summarize the contributions of innate immunity to allograft rejection and discuss recent studies and emerging concepts in the targeted delivery of therapeutics to modulate the innate immune system to enhance allograft survival.

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Section: The Complement Cascadementioning

confidence: 99%