title: Targeted complement inhibition and microvasculature in transplants: a therapeutic perspective.
abstract: Active complement mediators play a key role in graft-versus-host diseases, but little attention has been given to the angiogenic balance and complement modulation during allograft acceptance. The complement cascade releases the powerful proinflammatory mediators C3a and C5a anaphylatoxins, C3b, C5b opsonins and terminal membrane attack complex into tissues, which are deleterious if unchecked. Blocking complement mediators has been considered to be a promising approach in the modern drug discovery plan, and a significant number of therapeutic alternatives have been developed to dampen complement activation and protect host cells. Numerous immune cells, especially macrophages, develop both anaphylatoxin and opsonin receptors on their cell surface and their binding affects the macrophage phenotype and their angiogenic properties. This review discusses the mechanism that complement contributes to angiogenic injury, and the development of future therapeutic targets by antagonizing activated complement mediators to preserve microvasculature in rejecting the transplanted organ.
authors.affiliation: Organ Transplant Centre, Comparative Medicine Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia.
authors.forename: M A
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Hsu
authors.affiliation: Organ Transplant Centre, Comparative Medicine Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia.
authors.forename: A M
authors.initials: AM
authors.lastname: Assiri
authors.affiliation: Organ Transplant Centre, Comparative Medicine Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia.
authors.forename: D C
authors.initials: DC
authors.lastname: Broering
mesh_terms: D003167:Complement Activation; D015938:Complement Membrane Attack Complex / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D006084:Graft Rejection / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000628:therapy; D006801:Humans; D008264:Macrophages / Q000276:immunology; D055806:Microvessels / Q000502:physiology*; D058990:Molecular Targeted Therapy; D018919:Neovascularization, Physiologic / Q000276:immunology; D019737:Transplants / Q000098:blood supply* / Q000276:immunology*
chemical_list: D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins
keywords: allograft rejection; angiogenesis; complement inhibition; complement-mediated injury