title: Demonstration of early functional compromise of bone marrow derived hematopoietic progenitor cells during bovine neonatal pancytopenia through in vitro culture of bone marrow biopsies.
abstract: BACKGROUND
  Bovine neonatal pancytopenia (BNP) is a syndrome characterised by thrombocytopenia associated with marked bone marrow destruction in calves, widely reported since 2007 in several European countries and since 2011 in New Zealand. The disease is epidemiologically associated with the use of an inactivated bovine virus diarrhoea (BVD) vaccine and is currently considered to be caused by absorption of colostral antibody produced by some vaccinated cows ("BNP dams"). Alloantibodies capable of binding to the leukocyte surface have been detected in BNP dams and antibodies recognising bovine MHC class I and β-2-microglobulin have been detected in vaccinated cattle. In this study, calves were challenged with pooled colostrum collected from BNP dams or from non-BNP dams and their bone marrow hematopoietic progenitor cells (HPC) cultured in vitro from sternal biopsies taken at 24 hours and 6 days post-challenge.
  
  
  RESULTS
  Clonogenic assay demonstrated that CFU-GEMM (colony forming unit-granulocyte/erythroid/macrophage/megakaryocyte; pluripotential progenitor cell) colony development was compromised from HPCs harvested as early as 24 hour post-challenge. By 6 days post challenge, HPCs harvested from challenged calves failed to develop CFU-E (erythroid) colonies and the development of both CFU-GEMM and CFU-GM (granulocyte/macrophage) was markedly reduced.
  
  
  CONCLUSIONS
  This study suggests that the bone marrow pathology and clinical signs associated with BNP are related to an insult which compromises the pluripotential progenitor cell within the first 24 hours of life but that this does not initially include all cell types.
authors.affiliation: Moredun Research Institute, International Research Centre, Pentlands Science Park, Bush Loan, Midlothian, EH26 0PZ, UK.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Laming
authors.forename: Eleonora
authors.initials: E
authors.lastname: Melzi
authors.forename: Sandra F E
authors.initials: SF
authors.lastname: Scholes
authors.forename: Maira
authors.initials: M
authors.lastname: Connelly
authors.forename: Charlotte R
authors.initials: CR
authors.lastname: Bell
authors.forename: Keith T
authors.initials: KT
authors.lastname: Ballingall
authors.forename: Mark P
authors.initials: MP
authors.lastname: Dagleish
authors.forename: Mara S
authors.initials: MS
authors.lastname: Rocchi
authors.forename: Kim
authors.initials: K
authors.lastname: Willoughby
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002417:Cattle; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003126:Colostrum / Q000276:immunology; D001908:Diarrhea Viruses, Bovine Viral / Q000276:immunology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010198:Pancytopenia / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010865:Pilot Projects; D039904:Pluripotent Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D013577:Syndrome; D013921:Thrombocytopenia / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014611:Vaccination; D014612:Vaccines / Q000276:immunology
chemical_list: D015415:Biomarkers; D014612:Vaccines