Defective glycosylphosphatidylinositol anchor synthesis in paroxysmal nocturnal hemoglobinuria granulocytes

John F. Mahoney, Masaharu Urakaze, Sharon Hall, Rita DeGasperi, Hui Ming Chang, Eiji Sugiyama, Christopher D. Warren, Michael J Borowitz, Anne Nicholson-Weller, Wendell F. Rosse, Edward T H Yeh

Research output: Contribution to journalArticle

Abstract

To investigate the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor in the granulocytes of paroxysmal nocturnal hemoglobinuria (PNH), the glycolipids of granulocytes from PNH patients and normal volunteers were biosynthetically labeled with [3H]mannose in the presence of tunicamycin. Extracted glycolipids were examined by thin-layer chromatography and compared with known biosynthetic intermediates. Normal granulocytes consistently showed [3H]mannose incorporation into the complete GPI core, several GPI biosynthetic intermediates, and dolichol phosphate mannose (DPM). The granulocytes of 10 patients with PNH that had no expression of CD55 and CD59 on greater than 95% of the cells were able to incorporate [3H]mannose into DPM, but were not able to incorporate detectable amounts into the complete GPI core. Thus, PNH granulocytes do not synthesize detectable amounts of the complete GPI core and this defect likely accounts for the absence of GPI-linked membrane proteins on hematopoietic cells in this syndrome.

Original languageEnglish (US)
Pages (from-to)1400-1403
Number of pages4
JournalBlood
Volume79
Issue number6
StatePublished - Mar 15 1992
Externally publishedYes

Fingerprint

Paroxysmal Hemoglobinuria
Glycosylphosphatidylinositols
Mannose
Granulocytes
Dolichol Phosphates
Glycolipids
GPI-Linked Proteins
Tunicamycin
Thin layer chromatography
Thin Layer Chromatography
Biosynthesis
Healthy Volunteers
Membrane Proteins
Defects

ASJC Scopus subject areas

  • Hematology

Cite this

Mahoney, J. F., Urakaze, M., Hall, S., DeGasperi, R., Chang, H. M., Sugiyama, E., ... Yeh, E. T. H. (1992). Defective glycosylphosphatidylinositol anchor synthesis in paroxysmal nocturnal hemoglobinuria granulocytes. Blood, 79(6), 1400-1403.

Defective glycosylphosphatidylinositol anchor synthesis in paroxysmal nocturnal hemoglobinuria granulocytes. / Mahoney, John F.; Urakaze, Masaharu; Hall, Sharon; DeGasperi, Rita; Chang, Hui Ming; Sugiyama, Eiji; Warren, Christopher D.; Borowitz, Michael J; Nicholson-Weller, Anne; Rosse, Wendell F.; Yeh, Edward T H.

In: Blood, Vol. 79, No. 6, 15.03.1992, p. 1400-1403.

Research output: Contribution to journalArticle

Mahoney, JF, Urakaze, M, Hall, S, DeGasperi, R, Chang, HM, Sugiyama, E, Warren, CD, Borowitz, MJ, Nicholson-Weller, A, Rosse, WF & Yeh, ETH 1992, 'Defective glycosylphosphatidylinositol anchor synthesis in paroxysmal nocturnal hemoglobinuria granulocytes', Blood, vol. 79, no. 6, pp. 1400-1403.
Mahoney JF, Urakaze M, Hall S, DeGasperi R, Chang HM, Sugiyama E et al. Defective glycosylphosphatidylinositol anchor synthesis in paroxysmal nocturnal hemoglobinuria granulocytes. Blood. 1992 Mar 15;79(6):1400-1403.
Mahoney, John F. ; Urakaze, Masaharu ; Hall, Sharon ; DeGasperi, Rita ; Chang, Hui Ming ; Sugiyama, Eiji ; Warren, Christopher D. ; Borowitz, Michael J ; Nicholson-Weller, Anne ; Rosse, Wendell F. ; Yeh, Edward T H. / Defective glycosylphosphatidylinositol anchor synthesis in paroxysmal nocturnal hemoglobinuria granulocytes. In: Blood. 1992 ; Vol. 79, No. 6. pp. 1400-1403.
@article{33299cbd0e7045969691c752353b1c45,
title = "Defective glycosylphosphatidylinositol anchor synthesis in paroxysmal nocturnal hemoglobinuria granulocytes",
abstract = "To investigate the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor in the granulocytes of paroxysmal nocturnal hemoglobinuria (PNH), the glycolipids of granulocytes from PNH patients and normal volunteers were biosynthetically labeled with [3H]mannose in the presence of tunicamycin. Extracted glycolipids were examined by thin-layer chromatography and compared with known biosynthetic intermediates. Normal granulocytes consistently showed [3H]mannose incorporation into the complete GPI core, several GPI biosynthetic intermediates, and dolichol phosphate mannose (DPM). The granulocytes of 10 patients with PNH that had no expression of CD55 and CD59 on greater than 95{\%} of the cells were able to incorporate [3H]mannose into DPM, but were not able to incorporate detectable amounts into the complete GPI core. Thus, PNH granulocytes do not synthesize detectable amounts of the complete GPI core and this defect likely accounts for the absence of GPI-linked membrane proteins on hematopoietic cells in this syndrome.",
author = "Mahoney, {John F.} and Masaharu Urakaze and Sharon Hall and Rita DeGasperi and Chang, {Hui Ming} and Eiji Sugiyama and Warren, {Christopher D.} and Borowitz, {Michael J} and Anne Nicholson-Weller and Rosse, {Wendell F.} and Yeh, {Edward T H}",
year = "1992",
month = "3",
day = "15",
language = "English (US)",
volume = "79",
pages = "1400--1403",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "6",

}

TY - JOUR

T1 - Defective glycosylphosphatidylinositol anchor synthesis in paroxysmal nocturnal hemoglobinuria granulocytes

AU - Mahoney, John F.

AU - Urakaze, Masaharu

AU - Hall, Sharon

AU - DeGasperi, Rita

AU - Chang, Hui Ming

AU - Sugiyama, Eiji

AU - Warren, Christopher D.

AU - Borowitz, Michael J

AU - Nicholson-Weller, Anne

AU - Rosse, Wendell F.

AU - Yeh, Edward T H

PY - 1992/3/15

Y1 - 1992/3/15

N2 - To investigate the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor in the granulocytes of paroxysmal nocturnal hemoglobinuria (PNH), the glycolipids of granulocytes from PNH patients and normal volunteers were biosynthetically labeled with [3H]mannose in the presence of tunicamycin. Extracted glycolipids were examined by thin-layer chromatography and compared with known biosynthetic intermediates. Normal granulocytes consistently showed [3H]mannose incorporation into the complete GPI core, several GPI biosynthetic intermediates, and dolichol phosphate mannose (DPM). The granulocytes of 10 patients with PNH that had no expression of CD55 and CD59 on greater than 95% of the cells were able to incorporate [3H]mannose into DPM, but were not able to incorporate detectable amounts into the complete GPI core. Thus, PNH granulocytes do not synthesize detectable amounts of the complete GPI core and this defect likely accounts for the absence of GPI-linked membrane proteins on hematopoietic cells in this syndrome.

AB - To investigate the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor in the granulocytes of paroxysmal nocturnal hemoglobinuria (PNH), the glycolipids of granulocytes from PNH patients and normal volunteers were biosynthetically labeled with [3H]mannose in the presence of tunicamycin. Extracted glycolipids were examined by thin-layer chromatography and compared with known biosynthetic intermediates. Normal granulocytes consistently showed [3H]mannose incorporation into the complete GPI core, several GPI biosynthetic intermediates, and dolichol phosphate mannose (DPM). The granulocytes of 10 patients with PNH that had no expression of CD55 and CD59 on greater than 95% of the cells were able to incorporate [3H]mannose into DPM, but were not able to incorporate detectable amounts into the complete GPI core. Thus, PNH granulocytes do not synthesize detectable amounts of the complete GPI core and this defect likely accounts for the absence of GPI-linked membrane proteins on hematopoietic cells in this syndrome.

UR - http://www.scopus.com/inward/record.url?scp=0026600639&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026600639&partnerID=8YFLogxK

M3 - Article

C2 - 1372185

AN - SCOPUS:0026600639

VL - 79

SP - 1400

EP - 1403

JO - Blood

JF - Blood

SN - 0006-4971

IS - 6

ER -