Expression of the serine protease inhibitor neuroserpin in cells of the human myeloid lineage.
Myeloid progenitors in the bone marrow differentiate into most of the major cell types of the immune system, including macrophages and dendritic cells. These cells play important roles in both innate and adaptive immunity. They express a number of proteases and protease inhibitors including members of the serine proteinase inhibitor or serpin superfamily. In this study we report the differential expression of neuroserpin in cells of the human myeloid lineage. Neuroserpin was highly expressed and secreted following the differentiation of monocytes to macrophages and dendritic cells. Activation of dendritic cells with lipopolysaccharide resulted in increased neuroserpin mRNA levels but no neuroserpin secretion. Confocal immunofluorescence microscopy showed neuroserpin was differentially localised in human myeloid cells. In macrophages and dendritic cells it was concentrated in vesicles located in close proximity to the plasma membrane. The majority of activated dendritic cells also exhibited an intracellular focal concentration of neuroserpin which co-localised with the lysosomal/late endosomal marker LAMP-1. As neuroserpin inhibits tissue plasminogen activator, a comparative analysis of tPA and plasminogen activator inhibitor-1 (PAI-1) expression was undertaken. This analysis revealed differential expression of PAI-1 and neuroserpin suggesting they may have different functions in human immune cells.
Kennedy
Sarah A
SA
School of Biological Sciences, Level 4, Thomas Building, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand.
van Diepen
Angela C
AC
van den Hurk
Cecilia M
CM
Coates
Leigh C
LC
Lee
Tet Woo
TW
Ostrovsky
Lena L
LL
Miranda
Elena
E
Perez
Juan
J
Davies
Mark J
MJ
Lomas
David A
DA
Dunbar
P Rod
PR
Birch
Nigel P
NP
D015153:Blotting, Western; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D008070:Lipopolysaccharides; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D018613:Microscopy, Confocal; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D022423:Myeloid Cells / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D015854:Up-Regulation; D000097522:Neuroserpin
D008070:Lipopolysaccharides; D009479:Neuropeptides; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; D015843:Serpins; D010959:Tissue Plasminogen Activator; D000097522:Neuroserpin