title: Restoration of neutrophil and platelet function in feline Chediak-Higashi syndrome by bone marrow transplantation.
abstract: Allogeneic bone marrow transplantation (BMT) was successfully performed in four Chediak-Higashi (CHS) syndrome affected cats. Preparatory regimens included selective intestinal flora decontamination, fractionated total body irradiation for myeloablation, and prophylactic treatment for graft-versus-host disease with cyclosporin A. Neutrophil chemotaxis under-agarose and whole-blood platelet aggregation/secretion were characterized prior to BMT and after engraftment of donor-origin marrow cells. Liver and kidney biopsies were obtained and evaluated by light and electron microscopy before, and at 6 months post-BMT to determine what effect BMT might have on abnormal lysosome fusion in hepatocytes and renal tubule cells. The platelet storage pool defect was resolved by day 40 post-BMT. In vitro neutrophil migration in all cats appeared to improve with time after BMT and complete restoration was evident by day 175 post-BMT. No apparent differences were evident in either the liver or the kidney at 6 months post-BMT. One cat developed seizures and one developed posterior paresis 5 months post-BMT; neurologic impairment ultimately resulted in death of two cats at 6 and 8 months post-BMT, respectively. Neurologic lesions in both cats were characterized by non-suppurative encephalitis. Allogeneic BMT successfully corrected the neutrophil migration defect and platelet storage pool deficiency but had no effect on lysosome distribution in liver and kidney cells of CHS cats.
authors.affiliation: Department of Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523.
authors.forename: S P
authors.initials: SP
authors.lastname: Colgan
authors.forename: M A
authors.initials: MA
authors.lastname: Hull-Thrall
authors.forename: P W
authors.initials: PW
authors.lastname: Gasper
authors.forename: D H
authors.initials: DH
authors.lastname: Gould
authors.forename: B J
authors.initials: BJ
authors.lastname: Rose
authors.forename: R
authors.initials: R
authors.lastname: Fulton
authors.forename: A M
authors.initials: AM
authors.lastname: Blanquaert
authors.forename: W J
authors.initials: WJ
authors.lastname: Bruyninckx
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000473:pathology / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000473:pathology / Q000502:physiology*; D002371:Cat Diseases / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D002415:Cats; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002609:Chediak-Higashi Syndrome / Q000473:pathology / Q000601:surgery / Q000662:veterinary*; D003524:Cyclosporins / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy; D007668:Kidney / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D008099:Liver / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009504:Neutrophils / Q000473:pathology / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D010981:Platelet Storage Pool Deficiency / Q000473:pathology / Q000601:surgery / Q000662:veterinary; D014916:Whole-Body Irradiation
chemical_list: D003524:Cyclosporins; D000255:Adenosine Triphosphate