| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Published online before print June 7, 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1-acid glycoprotein is synthesized in myelocytes, stored in secondary granules, and released by activated neutrophils
* The Granulocyte Research Laboratory, Department of Hematology, and
Section of Gene Therapy Research, Department of Clinical Biochemistry, Rigshospitalet, and
Department of Hematology, Herlev Hospital, University of Copenhagen, Denmark,
Department of Hematology, Royal Manchester Children’s Hospital, United Kingdom;
¶ Booth Hall Children’s Hospital, University of Manchester, United Kingdom;
|| Division of Hematology/Oncology, Cedars-Sinai Medical Center, Burns and Allan Research Institute, University of California, Los Angeles, School of Medicine; and
** Department of Cell Biology, The Netherlands Cancer Institute, Amsterdam
1 Correspondence: Department of Hematology-4042, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen-Ø, Denmark. E-mail: borregaard{at}rh.dk
-1-Acid glycoprotein (AGP) is an acute-phase protein produced by hepatocytes and secreted into plasma in response to infection/injury. We recently assessed the transcriptional program of terminal granulocytic differentiation by microarray analysis of bone marrow (BM) populations highly enriched in promyelocytes, myelocytes/metamyelocytes (MYs), and BM neutrophils. These analyses demonstrated a transient, high mRNA expression of genuine secondary/tertiary granule proteins and AGP in MYs. In agreement with this, immunocytochemistry revealed the presence of AGP protein and the secondary granule protein lactoferrin in cells from the MY stage and throughout granulocytic differentiation. Immunoelectron microscopy demonstrated the colocalization of AGP and lactoferrin in secondary granules of neutrophils. This finding was substantiated by the failure to detect AGP and lactoferrin in blood cells from a patient with secondary/tertiary (specific) granule deficiency. In addition, Western blot analysis of subcellular fractions isolated from neutrophils revealed that neutrophil-derived AGP, localized in secondary granules, was abundant and highly glycosylated compared with endocytosed, plasma-derived AGP localized in secretory vesicles. Exocytosis studies further demonstrated a marked release of AGP and lactoferrin by activated neutrophils. Finally, induction of CCAAT/enhancer-binding protein (C/EBP)-
in a myeloid cell line was shown to increase AGP transcript levels, indicating that AGP expression in myeloid cells, like in hepatocytes, is partially regulated by members of the C/EBP family. Overall, these findings define AGP as a genuine secondary granule protein of neutrophils. Hence, neutrophils, which constitute the first line of defense, are likely to serve as the primary local source of AGP at sites of infection or injury.
Key Words: granulocytes • granule proteins • specific granule deficiency • acute-phase proteins • C/EBP
This article has been cited by other articles:
|
|
 |
|
  P. Gunnarsson, L. Levander, P. Pahlsson, and M. Grenegard The acute-phase protein {alpha}1-acid glycoprotein (AGP) induces rises in cytosolic Ca2+ in neutrophil granulocytes via sialic acid binding immunoglobulin-like lectins (Siglecs) FASEB J, December 1, 2007; 21(14): 4059 - 4069. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Novak, B. A. Donoval, P. J. Graham, L. A. Boksa, G. Spear, R. C. Hershow, H. Y. Chen, and A. Landay Cervicovaginal Levels of Lactoferrin, Secretory Leukocyte Protease Inhibitor, and RANTES and the Effects of Coexisting Vaginoses in Human Immunodeficiency Virus (HIV)-Seronegative Women with a High Risk of Heterosexual Acquisition of HIV Infection Clin. Vaccine Immunol., September 1, 2007; 14(9): 1102 - 1107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Jacobsen, K. Theilgaard-Monch, E. I. Christensen, and N. Borregaard Arginase 1 is expressed in myelocytes/metamyelocytes and localized in gelatinase granules of human neutrophils Blood, April 1, 2007; 109(7): 3084 - 3087. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
