title: Terminal complement components mediate release of von Willebrand factor and adhesion of platelets in arteries of allografts.
abstract: BACKGROUND
  Both humoral and cellular immune responses can cause arterial injury in organ transplants, but the manifestations of these different inflammatory mechanisms have not been dissected fully. The present study was designed to define the effects of the terminal complement components on arterial injury in vivo.
  
  
  METHODS
  The authors have developed congenic rat strains with a C6 deficiency. The absence of C6 terminates the cascade of complement after C5 cleavage and prevents the assembly of the membrane attack complex. Hearts were transplanted from PVG.1A (RT1) rats to major histocompatibility complex-incompatible C6-deficient (C6-) or C6-sufficient (C6+) PVG.1U (RT1) rats.
  
  
  RESULTS
  PVG.1A (C6-) cardiac grafts were rejected acutely (6-7 days) by untreated PVG.1U (C6+) recipients but survived significantly longer in PVG.1U (C6-) recipients (8 to >30 days). Arteries of cardiac allografts in C6+ recipients demonstrated extensive endothelial injury evidenced by release of von Willebrand factor (vWF) and accompanied by platelet aggregation. In contrast, vWF was retained in Weibel-Palade storage granules of arterial endothelial cells in cardiac allografts that were rejected by C6- recipients. In the absence of C6, intimal alterations were limited to lifting of endothelial cells from supporting stroma by infiltrating mononuclear cells, duplicating the clinical lesion described as endotheliitis or intimal arteritis. Delaying graft rejection with a short course of cyclosporine did not decrease vWF release and platelet aggregation in PVG.1U (C6+) recipients.
  
  
  CONCLUSIONS
  Mononuclear cell infiltration of the arterial intima occurs in the absence of C6, but C6 deficiency limits the release of vWF from arterial endothelial cells.
authors.affiliation: Department of Pathology, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ota
authors.forename: Karen
authors.initials: K
authors.lastname: Fox-Talbot
authors.forename: Weimin
authors.initials: W
authors.lastname: Hu
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Qian
authors.forename: Fred
authors.initials: F
authors.lastname: Sanfilippo
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: William M
authors.initials: WM
authors.lastname: Baldwin
mesh_terms: D000818:Animals; D015933:Complement C3d / Q000032:analysis; D003183:Complement C6 / Q000172:deficiency; D003165:Complement System Proteins / Q000502:physiology*; D005260:Female; D016027:Heart Transplantation / Q000473:pathology / Q000502:physiology*; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007518:Isoantibodies / Q000097:blood*; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D051381:Rats; D011919:Rats, Inbred Strains; D014184:Transplantation, Homologous / Q000473:pathology / Q000502:physiology; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D003183:Complement C6; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007518:Isoantibodies; D014841:von Willebrand Factor; D015933:Complement C3d; D003165:Complement System Proteins