title: Altered natural killer cell subset homeostasis and defective chemotactic responses in paroxysmal nocturnal hemoglobinuria.
abstract: In paroxysmal nocturnal hemoglobinuria (PNH), hematopoietic cells lacking glycosylphosphatidylinositol (GPI)-linked proteins on their surface (GPI(neg)) exist alongside normal (GPI+) cells. Analysis of natural killer (NK) cell subsets in 47 PNH patients revealed that the ratio of CD56(bright):CD56(dim) NK cells differed in the GPI+ and GPI(neg) populations, with GPI(neg)CD56(bright) NK cells significantly more abundant in peripheral blood than their normal GPI+ counterparts. Indeed, GPI+CD56(bright) NK cells were not detected in the peripheral blood of some patients, suggesting their trafficking to a niche unavailable to the GPI(neg)CD56(bright) NK cell population. Defective cellular trafficking in this disease was supported by findings showing differential chemokine receptor expression between GPI+ and GPI(neg) NK cells and impaired stromal cell-derived factor 1 (SDF-1)-induced chemotaxis of GPI(neg) NK cells. Our results indicate a role for GPI-linked proteins in NK cell subset homeostasis and suggest that differential chemokine responses might contribute to the balance of GPI+ and GPI(neg) populations in this disease.
authors.affiliation: Leeds Institute of Cancer and Pathology, and.
authors.forename: Yasser M
authors.initials: YM
authors.lastname: El-Sherbiny
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kelly
authors.forename: Anita
authors.initials: A
authors.lastname: Hill
authors.forename: Gina M
authors.initials: GM
authors.lastname: Doody
authors.forename: Peter
authors.initials: P
authors.lastname: Hillmen
authors.forename: Graham P
authors.initials: GP
authors.lastname: Cook
mesh_terms: D019002:CD56 Antigen / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000276:immunology / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000276:immunology* / Q000473:pathology; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism
chemical_list: D019002:CD56 Antigen; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D058851:GPI-Linked Proteins; D019718:Receptors, CXCR4