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Porcine sialoadhesin (CD169/Siglec-1) is an endocytic receptor that allows targeted delivery of toxins and antigens to macrophages

Peter Delputte UGent, Hanne Van Gorp UGent, Herman Favoreel UGent, Inge Hoebeke UGent, Iris Delrue UGent, Hannah Dewerchin UGent, Frederik Verdonck UGent, Bruno Verhasselt UGent, Eric Cox UGent and Hans Nauwynck UGent (2011) PLOS ONE. 6(2).
abstract
Sialoadhesin is exclusively expressed on specific subpopulations of macrophages. Since sialoadhesin-positive macrophages are involved in inflammatory autoimmune diseases, such as multiple sclerosis, and potentially in the generation of immune responses, targeted delivery of drugs, toxins or antigens via sialoadhesin-specific immunoconjugates may prove a useful therapeutic strategy. Originally, sialoadhesin was characterized as a lymphocyte adhesion molecule, though recently its involvement in internalization of sialic acid carrying pathogens was shown, suggesting that sialoadhesin is an endocytic receptor. In this report, we show that porcine sialoadhesin-specific antibodies and F(ab')(2) fragments trigger sialoadhesin internalization, both in primary porcine macrophages and in cells expressing recombinant porcine sialoadhesin. Using chemical inhibitors, double immunofluorescence stainings and dominant-negative constructs, porcine sialoadhesin internalization was shown to be clathrin-and Eps15-dependent and to result in targeting to early endosomes but not lysosomes. Besides characterizing the sialoadhesin endocytosis mechanism, two sialoadhesin-specific immunoconjugates were evaluated. We observed that porcine sialoadhesin-specific immunotoxins efficiently kill sialoadhesin-expressing macrophages. Furthermore, porcine sialoadhesin-specific albumin immunoconjugates were shown to be internalized in macrophages and immunization with these immunoconjugates resulted in a rapid and robust induction of albumin-specific antibodies, this compared to immunization with albumin alone. Together, these data expand sialoadhesin functionality and show that it can function as an endocytic receptor, a feature that cannot only be misused by sialic acid carrying pathogens, but that may also be used for specific targeting of toxins or antigens to sialoadhesin-expressing macrophages.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
ALVEOLAR MACROPHAGES, B-CELL, MONOCLONAL-ANTIBODIES, MEDIATED ENDOCYTOSIS, TISSUE MACROPHAGES, SIALIC-ACID, PSEUDORABIES VIRUS, RESPIRATORY SYNDROME VIRUS, LIPID RAFT ASSOCIATION, ACID-BINDING-RECEPTOR
journal title
PLOS ONE
PLoS One
volume
6
issue
2
article_number
e16827
pages
12 pages
Web of Science type
Article
Web of Science id
000287392700025
JCR category
BIOLOGY
JCR impact factor
4.092 (2011)
JCR rank
12/84 (2011)
JCR quartile
1 (2011)
ISSN
1932-6203
DOI
10.1371/journal.pone.0016827
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
1205421
handle
http://hdl.handle.net/1854/LU-1205421
date created
2011-04-08 15:59:37
date last changed
2012-03-29 09:02:09
@article{1205421,
  abstract     = {Sialoadhesin is exclusively expressed on specific subpopulations of macrophages. Since sialoadhesin-positive macrophages are involved in inflammatory autoimmune diseases, such as multiple sclerosis, and potentially in the generation of immune responses, targeted delivery of drugs, toxins or antigens via sialoadhesin-specific immunoconjugates may prove a useful therapeutic strategy. Originally, sialoadhesin was characterized as a lymphocyte adhesion molecule, though recently its involvement in internalization of sialic acid carrying pathogens was shown, suggesting that sialoadhesin is an endocytic receptor. In this report, we show that porcine sialoadhesin-specific antibodies and F(ab')(2) fragments trigger sialoadhesin internalization, both in primary porcine macrophages and in cells expressing recombinant porcine sialoadhesin. Using chemical inhibitors, double immunofluorescence stainings and dominant-negative constructs, porcine sialoadhesin internalization was shown to be clathrin-and Eps15-dependent and to result in targeting to early endosomes but not lysosomes. Besides characterizing the sialoadhesin endocytosis mechanism, two sialoadhesin-specific immunoconjugates were evaluated. We observed that porcine sialoadhesin-specific immunotoxins efficiently kill sialoadhesin-expressing macrophages. Furthermore, porcine sialoadhesin-specific albumin immunoconjugates were shown to be internalized in macrophages and immunization with these immunoconjugates resulted in a rapid and robust induction of albumin-specific antibodies, this compared to immunization with albumin alone. Together, these data expand sialoadhesin functionality and show that it can function as an endocytic receptor, a feature that cannot only be misused by sialic acid carrying pathogens, but that may also be used for specific targeting of toxins or antigens to sialoadhesin-expressing macrophages.},
  articleno    = {e16827},
  author       = {Delputte, Peter and Van Gorp, Hanne and Favoreel, Herman and Hoebeke, Inge and Delrue, Iris and Dewerchin, Hannah and Verdonck, Frederik and Verhasselt, Bruno and Cox, Eric and Nauwynck, Hans},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keyword      = {ALVEOLAR MACROPHAGES,B-CELL,MONOCLONAL-ANTIBODIES,MEDIATED ENDOCYTOSIS,TISSUE MACROPHAGES,SIALIC-ACID,PSEUDORABIES VIRUS,RESPIRATORY SYNDROME VIRUS,LIPID RAFT ASSOCIATION,ACID-BINDING-RECEPTOR},
  language     = {eng},
  number       = {2},
  pages        = {12},
  title        = {Porcine sialoadhesin (CD169/Siglec-1) is an endocytic receptor that allows targeted delivery of toxins and antigens to macrophages},
  url          = {http://dx.doi.org/10.1371/journal.pone.0016827},
  volume       = {6},
  year         = {2011},
}

Chicago
Delputte, Peter, Hanne Van Gorp, Herman Favoreel, Inge Hoebeke, Iris Delrue, Hannah Dewerchin, Frederik Verdonck, Bruno Verhasselt, Eric Cox, and Hans Nauwynck. 2011. “Porcine Sialoadhesin (CD169/Siglec-1) Is an Endocytic Receptor That Allows Targeted Delivery of Toxins and Antigens to Macrophages.” Plos One 6 (2).
APA
Delputte, P., Van Gorp, H., Favoreel, H., Hoebeke, I., Delrue, I., Dewerchin, H., Verdonck, F., et al. (2011). Porcine sialoadhesin (CD169/Siglec-1) is an endocytic receptor that allows targeted delivery of toxins and antigens to macrophages. PLOS ONE, 6(2).
Vancouver
1.
Delputte P, Van Gorp H, Favoreel H, Hoebeke I, Delrue I, Dewerchin H, et al. Porcine sialoadhesin (CD169/Siglec-1) is an endocytic receptor that allows targeted delivery of toxins and antigens to macrophages. PLOS ONE. 2011;6(2).
MLA
Delputte, Peter, Hanne Van Gorp, Herman Favoreel, et al. “Porcine Sialoadhesin (CD169/Siglec-1) Is an Endocytic Receptor That Allows Targeted Delivery of Toxins and Antigens to Macrophages.” PLOS ONE 6.2 (2011): n. pag. Print.