title: The characteristics of hematopoietic stem cells from autoimmune-prone mice and the role of neural cell adhesion molecules in abnormal proliferation of these cells in MRL/lpr mice.
abstract: OBJECTIVE
  Using various animal models for autoimmune diseases, we have previously shown that such diseases are stem cell disorders.1 In order to understand how autoimmune diseases develop, we investigated the distinct qualitative differences between hematopoietic stem cells (HSC) from normal and autoimmune-prone mice.
  
  
  METHODS
  We studied the major histocompatibility complex (MHC) restriction between HSC and stromal cells in vitro and in vivo. We also examined the ability of HSC to adhere to a stromal cell line and, using flow cytometry, analyzed the expression of various adhesion molecules in HSC before and after the onset of autoimmune disease. In addition, the effect of antibodies to anti-adhesion molecules on the proliferation of HSC was investigated.
  
  
  RESULTS
  The abnormal HSC of MRL/lpr mice showed no MHC restriction (or preference) with stromal cells either in vitro or in vivo, although there was MHC restriction between normal HSC and stromal cells, as we previously reported.2,3 The abnormal HSC of MRL/lpr mice exhibited enhanced adhesion to stromal cells in vitro and expressed a higher amount of adhesion molecules such as neural cell adhesion molecule (NCAM). Interestingly, the proliferation of HSC in MRL/lpr mice was significantly suppressed by anti-NCAM monoclonaal antibodies.
  
  
  CONCLUSIONS
  Abnormal HSC of MRL/lpr mice are more resilient than normal HSC. Furthermore, among various adhesion molecules, only NCAM shows increased expression on HSC of MRL/lpr mice after the onset of autoimmune diseases, and these molecules contribute to the enhanced proliferation capacity of abnormal HSC in MRL/lpr mice. The present findings suggest that there are intrinsic qualitative differences between HSC from normal and autoimmune-prone MRL/lpr mice.
authors.affiliation: First Department of Pathology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hisha
authors.forename: Wenhao
authors.initials: W
authors.lastname: Cui
authors.forename: Changye
authors.initials: C
authors.lastname: Song
authors.forename: Tomomi
authors.initials: T
authors.lastname: Mizokami
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okazaki
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.forename: Junko
authors.initials: J
authors.lastname: Kato
authors.forename: Shiwen
authors.initials: S
authors.lastname: Jiang
authors.forename: Hongxue
authors.initials: H
authors.lastname: Fan
authors.forename: Susumu
authors.initials: S
authors.lastname: Ikehara
mesh_terms: D000367:Age Factors; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001853:Bone Marrow / Q000196:embryology; D002448:Cell Adhesion; D002455:Cell Division; D002478:Cells, Cultured / Q000166:cytology / Q000378:metabolism; D018920:Coculture Techniques; D003114:Colony-Forming Units Assay; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008181:Lupus Nephritis / Q000235:genetics; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr / Q000033:anatomy & histology* / Q000235:genetics / Q000276:immunology; D016688:Mice, Inbred NOD; D008814:Mice, Inbred NZB; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D011828:Radiation Chimera; D011836:Radiation Tolerance / Q000235:genetics; D017154:Stromal Cells / Q000276:immunology / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D006183:H-2 Antigens; D019006:Neural Cell Adhesion Molecules