Cargando…
Immune complexes from rheumatoid arthritis synovial fluid induce FcγRIIa dependent and rheumatoid factor correlated production of tumour necrosis factor-α by peripheral blood mononuclear cells
Immune complexes (ICs) can induce production of cytokines by peripheral blood mononuclear cells via Fc receptors. Rheumatoid factor (RF) develop in response to ICs in many clinical and experimental settings. We investigated whether and how polyethylene glycol (PEG) precipitated ICs from rheumatoid a...
Autores principales: | , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2006
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1526644/ https://www.ncbi.nlm.nih.gov/pubmed/16569263 http://dx.doi.org/10.1186/ar1926 |
_version_ | 1782128931727474688 |
---|---|
author | Mathsson, Linda Lampa, Jon Mullazehi, Mohammed Rönnelid, Johan |
author_facet | Mathsson, Linda Lampa, Jon Mullazehi, Mohammed Rönnelid, Johan |
author_sort | Mathsson, Linda |
collection | PubMed |
description | Immune complexes (ICs) can induce production of cytokines by peripheral blood mononuclear cells via Fc receptors. Rheumatoid factor (RF) develop in response to ICs in many clinical and experimental settings. We investigated whether and how polyethylene glycol (PEG) precipitated ICs from rheumatoid arthritis (RA) sera and synovial fluid (SF) can influence cytokine production by peripheral blood mononuclear cells. We also examined the relationship between RF and IC induced cytokine production. Parallel sera and SF from 47 RA patients and sera from 15 healthy control individuals were PEG precipitated. The precipitates were added to serum-free peripheral blood mononuclear cell cultures and tumour necrosis factor (TNF)-α levels were measured after 20 hours. In separate cell culture experiments FcγRIIa and FcγRIII were blocked and monocytes were depleted or enriched. RF in serum was determined by nephelometry, and IgG levels in precipitates and anti-cyclic citrullinated peptide antibodies in serum were measured using ELISA. Clinical data were collected from the patients' charts. In two separate investigations, we demonstrated a correlation between RF, PEG-precipitated IgG levels and induction of the proinflammatory cytokine TNF-α by PEG-precipitated SF ICs. No such correlation was found for serum ICs. TNF-α levels induced by SF precipitates, but not serum precipitates, correlated with the number of swollen and tender joints. Monocytes/macrophages were shown to be the main responder cells, and blockade of FcγRIIa, but not blockade of FcγRIII, inhibited TNF-α production in cultures stimulated with precipitated ICs. Anti-cyclic citrullinated peptide correlated with RF but exhibited no association with IgG content in PEG precipitates or with precipitate-induced TNF-α levels. These findings support the hypothesis that SF ICs and correlated RF production are directly linked to cytokine-dependent inflammation in RA. Suppression of monocytes/macrophages in RA joints or blockade of the primate-specific activating FcγRIIa receptor might be ways to reduce IC-induced TNF-α production in the joints of seropositive RA patients. |
format | Text |
id | pubmed-1526644 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-15266442006-08-04 Immune complexes from rheumatoid arthritis synovial fluid induce FcγRIIa dependent and rheumatoid factor correlated production of tumour necrosis factor-α by peripheral blood mononuclear cells Mathsson, Linda Lampa, Jon Mullazehi, Mohammed Rönnelid, Johan Arthritis Res Ther Research Article Immune complexes (ICs) can induce production of cytokines by peripheral blood mononuclear cells via Fc receptors. Rheumatoid factor (RF) develop in response to ICs in many clinical and experimental settings. We investigated whether and how polyethylene glycol (PEG) precipitated ICs from rheumatoid arthritis (RA) sera and synovial fluid (SF) can influence cytokine production by peripheral blood mononuclear cells. We also examined the relationship between RF and IC induced cytokine production. Parallel sera and SF from 47 RA patients and sera from 15 healthy control individuals were PEG precipitated. The precipitates were added to serum-free peripheral blood mononuclear cell cultures and tumour necrosis factor (TNF)-α levels were measured after 20 hours. In separate cell culture experiments FcγRIIa and FcγRIII were blocked and monocytes were depleted or enriched. RF in serum was determined by nephelometry, and IgG levels in precipitates and anti-cyclic citrullinated peptide antibodies in serum were measured using ELISA. Clinical data were collected from the patients' charts. In two separate investigations, we demonstrated a correlation between RF, PEG-precipitated IgG levels and induction of the proinflammatory cytokine TNF-α by PEG-precipitated SF ICs. No such correlation was found for serum ICs. TNF-α levels induced by SF precipitates, but not serum precipitates, correlated with the number of swollen and tender joints. Monocytes/macrophages were shown to be the main responder cells, and blockade of FcγRIIa, but not blockade of FcγRIII, inhibited TNF-α production in cultures stimulated with precipitated ICs. Anti-cyclic citrullinated peptide correlated with RF but exhibited no association with IgG content in PEG precipitates or with precipitate-induced TNF-α levels. These findings support the hypothesis that SF ICs and correlated RF production are directly linked to cytokine-dependent inflammation in RA. Suppression of monocytes/macrophages in RA joints or blockade of the primate-specific activating FcγRIIa receptor might be ways to reduce IC-induced TNF-α production in the joints of seropositive RA patients. BioMed Central 2006 2006-03-28 /pmc/articles/PMC1526644/ /pubmed/16569263 http://dx.doi.org/10.1186/ar1926 Text en Copyright © 2006 Mathsson et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Mathsson, Linda Lampa, Jon Mullazehi, Mohammed Rönnelid, Johan Immune complexes from rheumatoid arthritis synovial fluid induce FcγRIIa dependent and rheumatoid factor correlated production of tumour necrosis factor-α by peripheral blood mononuclear cells |
title | Immune complexes from rheumatoid arthritis synovial fluid induce FcγRIIa dependent and rheumatoid factor correlated production of tumour necrosis factor-α by peripheral blood mononuclear cells |
title_full | Immune complexes from rheumatoid arthritis synovial fluid induce FcγRIIa dependent and rheumatoid factor correlated production of tumour necrosis factor-α by peripheral blood mononuclear cells |
title_fullStr | Immune complexes from rheumatoid arthritis synovial fluid induce FcγRIIa dependent and rheumatoid factor correlated production of tumour necrosis factor-α by peripheral blood mononuclear cells |
title_full_unstemmed | Immune complexes from rheumatoid arthritis synovial fluid induce FcγRIIa dependent and rheumatoid factor correlated production of tumour necrosis factor-α by peripheral blood mononuclear cells |
title_short | Immune complexes from rheumatoid arthritis synovial fluid induce FcγRIIa dependent and rheumatoid factor correlated production of tumour necrosis factor-α by peripheral blood mononuclear cells |
title_sort | immune complexes from rheumatoid arthritis synovial fluid induce fcγriia dependent and rheumatoid factor correlated production of tumour necrosis factor-α by peripheral blood mononuclear cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1526644/ https://www.ncbi.nlm.nih.gov/pubmed/16569263 http://dx.doi.org/10.1186/ar1926 |
work_keys_str_mv | AT mathssonlinda immunecomplexesfromrheumatoidarthritissynovialfluidinducefcgriiadependentandrheumatoidfactorcorrelatedproductionoftumournecrosisfactorabyperipheralbloodmononuclearcells AT lampajon immunecomplexesfromrheumatoidarthritissynovialfluidinducefcgriiadependentandrheumatoidfactorcorrelatedproductionoftumournecrosisfactorabyperipheralbloodmononuclearcells AT mullazehimohammed immunecomplexesfromrheumatoidarthritissynovialfluidinducefcgriiadependentandrheumatoidfactorcorrelatedproductionoftumournecrosisfactorabyperipheralbloodmononuclearcells AT ronnelidjohan immunecomplexesfromrheumatoidarthritissynovialfluidinducefcgriiadependentandrheumatoidfactorcorrelatedproductionoftumournecrosisfactorabyperipheralbloodmononuclearcells |