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Elevated neutrophil membrane expression of proteinase 3 is dependent upon CD177 expression.

AbdGawad, Mohamed LU ; Gunnarsson, Lena LU ; Bengtsson, Anders LU ; Geborek, Pierre LU ; Nilsson, L; Segelmark, Mårten LU and Hellmark, Thomas LU (2010) In Clinical and Experimental Immunology 161. p.89-97
Abstract
Summary Proteinase 3 (PR3) is a major autoantigen in anti-neutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (AASV), and the proportion of neutrophils expressing PR3 on their membrane (mPR3(+)) is increased in AASV. We have shown recently that mPR3 and CD177 are expressed on the same cells in healthy individuals. In this study we try to elucidate mechanisms behind the increased mPR3 expression in AASV and its relationship to CD177. All neutrophils in all individuals were either double-positive or double-negative for mPR3 and CD177. The proportion of double-positive neutrophils was increased significantly in AASV and systemic lupus erythematosus patients. The proportion of mPR3(+)/CD177(+) cells was not correlated to... (More)
Summary Proteinase 3 (PR3) is a major autoantigen in anti-neutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (AASV), and the proportion of neutrophils expressing PR3 on their membrane (mPR3(+)) is increased in AASV. We have shown recently that mPR3 and CD177 are expressed on the same cells in healthy individuals. In this study we try to elucidate mechanisms behind the increased mPR3 expression in AASV and its relationship to CD177. All neutrophils in all individuals were either double-positive or double-negative for mPR3 and CD177. The proportion of double-positive neutrophils was increased significantly in AASV and systemic lupus erythematosus patients. The proportion of mPR3(+)/CD177(+) cells was not correlated to general inflammation, renal function, age, sex, drug treatment and levels of circulating PR3. AASV patients had normal levels of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. Pro-PR3 was found to constitute 10% of circulating PR3 but none of the mPR3. We found increased mRNA levels of both PR3 and CD177 in AASV, but they did not correlate with the proportion of double-positive cells. In cells sorted based on membrane expression, CD177-mRNA was several-fold higher in mPR3(+) cells. When exogenous PR3 was added to CD177-transfected U937 cells, only CD177(+) cells bound PR3 to their membrane. In conclusion, the increased membrane expression of PR3 found in AASV is not linked directly to circulating PR3 or PR3 gene transcription, but is dependent upon CD177 expression and correlated with the transcription of the CD177 gene. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical and Experimental Immunology
volume
161
pages
89 - 97
publisher
British Society for Immunology
external identifiers
  • wos:000278396900012
  • pmid:20491791
  • scopus:77953272041
ISSN
0009-9104
DOI
10.1111/j.1365-2249.2010.04154.x
language
English
LU publication?
yes
id
40a0c04a-9fca-451b-b638-f7cf5ea15b31 (old id 1610038)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20491791?dopt=Abstract
date added to LUP
2010-06-02 11:08:59
date last changed
2018-05-29 09:45:54
@article{40a0c04a-9fca-451b-b638-f7cf5ea15b31,
  abstract     = {Summary Proteinase 3 (PR3) is a major autoantigen in anti-neutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (AASV), and the proportion of neutrophils expressing PR3 on their membrane (mPR3(+)) is increased in AASV. We have shown recently that mPR3 and CD177 are expressed on the same cells in healthy individuals. In this study we try to elucidate mechanisms behind the increased mPR3 expression in AASV and its relationship to CD177. All neutrophils in all individuals were either double-positive or double-negative for mPR3 and CD177. The proportion of double-positive neutrophils was increased significantly in AASV and systemic lupus erythematosus patients. The proportion of mPR3(+)/CD177(+) cells was not correlated to general inflammation, renal function, age, sex, drug treatment and levels of circulating PR3. AASV patients had normal levels of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. Pro-PR3 was found to constitute 10% of circulating PR3 but none of the mPR3. We found increased mRNA levels of both PR3 and CD177 in AASV, but they did not correlate with the proportion of double-positive cells. In cells sorted based on membrane expression, CD177-mRNA was several-fold higher in mPR3(+) cells. When exogenous PR3 was added to CD177-transfected U937 cells, only CD177(+) cells bound PR3 to their membrane. In conclusion, the increased membrane expression of PR3 found in AASV is not linked directly to circulating PR3 or PR3 gene transcription, but is dependent upon CD177 expression and correlated with the transcription of the CD177 gene.},
  author       = {AbdGawad, Mohamed and Gunnarsson, Lena and Bengtsson, Anders and Geborek, Pierre and Nilsson, L and Segelmark, Mårten and Hellmark, Thomas},
  issn         = {0009-9104},
  language     = {eng},
  pages        = {89--97},
  publisher    = {British Society for Immunology},
  series       = {Clinical and Experimental Immunology},
  title        = {Elevated neutrophil membrane expression of proteinase 3 is dependent upon CD177 expression.},
  url          = {http://dx.doi.org/10.1111/j.1365-2249.2010.04154.x},
  volume       = {161},
  year         = {2010},
}