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p33 (gC1q Receptor) Prevents Cell Damage by Blocking the Cytolytic Activity of Antimicrobial Peptides.

Westman, Johannes LU ; Hansen, Finja LU ; Olin, Anders LU ; Mörgelin, Matthias LU ; Schmidtchen, Artur LU and Herwald, Heiko LU (2013) In Journal of Immunology 191(11). p.5714-5721
Abstract
The innate immune system is the first line of defense against invading microbes. Its specificity relies a great deal on host pattern recognition molecules that sense pathogen-associated molecular patterns of the invading pathogen. However, full protection is not always guaranteed, and some early defense mechanisms involved in bacterial killing, such as the complement system, can also exert cytolytic activity against host cells. Although these cascades are tightly regulated, the host has to take additional precautions to prevent its cell destruction. In this study, we describe that p33, a negatively charged surface protein found on endothelial cells also known as gC1q receptor, protects host cells from a cytolytic attack by antimicrobial... (More)
The innate immune system is the first line of defense against invading microbes. Its specificity relies a great deal on host pattern recognition molecules that sense pathogen-associated molecular patterns of the invading pathogen. However, full protection is not always guaranteed, and some early defense mechanisms involved in bacterial killing, such as the complement system, can also exert cytolytic activity against host cells. Although these cascades are tightly regulated, the host has to take additional precautions to prevent its cell destruction. In this study, we describe that p33, a negatively charged surface protein found on endothelial cells also known as gC1q receptor, protects host cells from a cytolytic attack by antimicrobial peptides (AMPs), such as LL37 and β-defensin 3. To this end, we characterized the interaction of p33 with AMPs by biochemical and functional means. Our data show that p33 forms a doughnut-shaped trimer that can bind up to three AMPs, and we identified a segment in p33 forming a β-sheet that mediates the binding to all AMPs. Moreover, our results show that p33 abolishes the lytic activity of AMPs at an equimolar ratio, and it protects endothelial cells and erythrocytes from AMP-induced lysis. Taken together, our data suggest a novel protective mechanism of p33 in modulating innate immune response by neutralizing cytotoxic AMPs at the host cell surface. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
191
issue
11
pages
5714 - 5721
publisher
American Association of Immunologists
external identifiers
  • wos:000327180600038
  • pmid:24174616
  • scopus:84888363080
ISSN
1550-6606
DOI
10.4049/jimmunol.1300596
language
English
LU publication?
yes
id
9b3ed3d1-2331-4916-a536-cff113f2cc32 (old id 4179960)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24174616?dopt=Abstract
date added to LUP
2013-12-04 20:06:35
date last changed
2019-09-04 02:21:19
@article{9b3ed3d1-2331-4916-a536-cff113f2cc32,
  abstract     = {The innate immune system is the first line of defense against invading microbes. Its specificity relies a great deal on host pattern recognition molecules that sense pathogen-associated molecular patterns of the invading pathogen. However, full protection is not always guaranteed, and some early defense mechanisms involved in bacterial killing, such as the complement system, can also exert cytolytic activity against host cells. Although these cascades are tightly regulated, the host has to take additional precautions to prevent its cell destruction. In this study, we describe that p33, a negatively charged surface protein found on endothelial cells also known as gC1q receptor, protects host cells from a cytolytic attack by antimicrobial peptides (AMPs), such as LL37 and β-defensin 3. To this end, we characterized the interaction of p33 with AMPs by biochemical and functional means. Our data show that p33 forms a doughnut-shaped trimer that can bind up to three AMPs, and we identified a segment in p33 forming a β-sheet that mediates the binding to all AMPs. Moreover, our results show that p33 abolishes the lytic activity of AMPs at an equimolar ratio, and it protects endothelial cells and erythrocytes from AMP-induced lysis. Taken together, our data suggest a novel protective mechanism of p33 in modulating innate immune response by neutralizing cytotoxic AMPs at the host cell surface.},
  author       = {Westman, Johannes and Hansen, Finja and Olin, Anders and Mörgelin, Matthias and Schmidtchen, Artur and Herwald, Heiko},
  issn         = {1550-6606},
  language     = {eng},
  number       = {11},
  pages        = {5714--5721},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {p33 (gC1q Receptor) Prevents Cell Damage by Blocking the Cytolytic Activity of Antimicrobial Peptides.},
  url          = {http://dx.doi.org/10.4049/jimmunol.1300596},
  volume       = {191},
  year         = {2013},
}