title: Reduced expression of osteonectin and increased natural killer cells may contribute to the pathophysiology of aplastic anemia.
abstract: Normal hematopoiesis involves complex interactions between hematopoietic cells and the bone marrow (BM) microenvironment. The exact causes and mechanisms involved in aplastic anemia (AA) are not known. For better understanding of the pathophysiology of AA, we investigated changes in the hematopoietic stem cell (HSC) compartment and the BM microenvironment in patients with AA by immunohistochemical analysis. A total of 10 AA patients and 10 controls were enrolled. Using BM biopsy specimen, we performed immunohistochemistry for osteopontin, osteonectin, osteocalcin, nestin, stromal-derived factor-1 (SDF-1), lymphocytes, macrophage, and HSCs. Numbers of HSCs and T/B lymphocytes were significantly lower in the AA specimens than the controls, and the AA specimens contained more natural killer cells (CD56(+) cells) (P < 0.01). The 2 groups had similar levels of expression of osteopontin, osteocalcin, nestin, and SDF-1. However, the number of osteonectin(+) cells in the AA specimens was significantly lower than in the control specimens (P<0.01). Our findings support the hypothesis that defects in the stromal cells contribute to the pathogenesis of AA by damaging HSC niche. Immune-mediated natural killer cells may also play a role in the pathogenesis of AA.
authors.affiliation: *Department of Pediatrics, College of Medicine Chungbuk National University, Cheongju Departments of †Laboratory Medicine ‡Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine §Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science & Engineering ∥Department of Pediatrics, Hanyang University Medical Center, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Meerim
authors.initials: M
authors.lastname: Park
authors.forename: Chan-Jeoung
authors.initials: CJ
authors.lastname: Park
authors.forename: Seongsoo
authors.initials: S
authors.lastname: Jang
authors.forename: Dae-Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Je-Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Kyoo-Hyung
authors.initials: KH
authors.lastname: Lee
authors.forename: Kyoujung
authors.initials: K
authors.lastname: Hwang
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000741:Anemia, Aplastic / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001854:Bone Marrow Cells / Q000502:physiology*; D002450:Cell Communication; D002452:Cell Count; D060833:Cellular Microenvironment; D054377:Chemokine CXCL12 / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015676:Osteonectin / Q000235:genetics / Q000378:metabolism*; D055153:Stem Cell Niche / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D059016:Tumor Microenvironment
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D015676:Osteonectin