N-Formyl Methionine Peptide-Mediated Neutrophil Activation in Systemic Sclerosis
(2022) In Frontiers in Immunology 12.- Abstract
Exaggerated neutrophil activation and formation of neutrophil extracellular traps (NETs) are reported in systemic sclerosis (SSc) but its involvement in SSc pathogenesis is not clear. In the present study we assessed markers of neutrophil activation and NET formation in SSc patients in relation to markers of inflammation and disease phenotype. Factors promoting neutrophil activation in SSc remain largely unknown. Among the neutrophil activating factors, mitochondrial-derived N-formyl methionine (fMet) has been reported in several autoinflammatory conditions. The aim of the current study is to assess whether SSc patients have elevated levels of fMet and the role of fMet in neutrophil-mediated inflammation on SSc pathogenesis. Markers of... (More)
Exaggerated neutrophil activation and formation of neutrophil extracellular traps (NETs) are reported in systemic sclerosis (SSc) but its involvement in SSc pathogenesis is not clear. In the present study we assessed markers of neutrophil activation and NET formation in SSc patients in relation to markers of inflammation and disease phenotype. Factors promoting neutrophil activation in SSc remain largely unknown. Among the neutrophil activating factors, mitochondrial-derived N-formyl methionine (fMet) has been reported in several autoinflammatory conditions. The aim of the current study is to assess whether SSc patients have elevated levels of fMet and the role of fMet in neutrophil-mediated inflammation on SSc pathogenesis. Markers of neutrophil activation (calprotectin, NETs) and levels of fMet were analyzed in plasma from two SSc cohorts (n=80 and n=20, respectively) using ELISA. Neutrophil activation assays were performed in presence or absence of formyl peptide receptor 1 (FPR1) inhibitor cyclosporin H. Elevated levels of calprotectin and NETs were observed in SSc patients as compared to healthy controls (p<0.0001) associating with SSc clinical disease characteristics. Further, SSc patients had elevated levels of circulating fMet as compared to healthy controls (p<0.0001). Consistent with a role for fMet-mediated neutrophil activation, fMet levels correlated with levels of calprotectin and NETs (r=0.34, p=0.002; r=0.29, p<0.01 respectively). Additionally, plasma samples from SSc patients with high levels of fMet induced de novo neutrophil activation through FPR1-dependent mechanisms. Our data for the first time implicates an important role for the mitochondrial component fMet in promoting neutrophil-mediated inflammation in SSc.
(Less)
- author
- Kuley, Runa ; Stultz, Ryan D. ; Duvvuri, Bhargavi ; Wang, Ting ; Fritzler, Marvin J. ; Hesselstrand, Roger LU ; Nelson, J. Lee and Lood, Christian LU
- organization
- publishing date
- 2022-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- autoimmunity, clinical biomarkers, mitochondrial peptides, neutrophil extracellular traps (NET), neutrophils (PMNs), systemic sclerosis
- in
- Frontiers in Immunology
- volume
- 12
- article number
- 785275
- publisher
- Frontiers Media S. A.
- external identifiers
-
- pmid:35069556
- scopus:85123123278
- ISSN
- 1664-3224
- DOI
- 10.3389/fimmu.2021.785275
- language
- English
- LU publication?
- yes
- id
- ce903d60-aad7-4eb2-b1b6-a5bf484eeaa4
- date added to LUP
- 2022-03-21 14:00:09
- date last changed
- 2024-04-24 04:26:24
@article{ce903d60-aad7-4eb2-b1b6-a5bf484eeaa4,
abstract = {{<p>Exaggerated neutrophil activation and formation of neutrophil extracellular traps (NETs) are reported in systemic sclerosis (SSc) but its involvement in SSc pathogenesis is not clear. In the present study we assessed markers of neutrophil activation and NET formation in SSc patients in relation to markers of inflammation and disease phenotype. Factors promoting neutrophil activation in SSc remain largely unknown. Among the neutrophil activating factors, mitochondrial-derived N-formyl methionine (fMet) has been reported in several autoinflammatory conditions. The aim of the current study is to assess whether SSc patients have elevated levels of fMet and the role of fMet in neutrophil-mediated inflammation on SSc pathogenesis. Markers of neutrophil activation (calprotectin, NETs) and levels of fMet were analyzed in plasma from two SSc cohorts (n=80 and n=20, respectively) using ELISA. Neutrophil activation assays were performed in presence or absence of formyl peptide receptor 1 (FPR1) inhibitor cyclosporin H. Elevated levels of calprotectin and NETs were observed in SSc patients as compared to healthy controls (p<0.0001) associating with SSc clinical disease characteristics. Further, SSc patients had elevated levels of circulating fMet as compared to healthy controls (p<0.0001). Consistent with a role for fMet-mediated neutrophil activation, fMet levels correlated with levels of calprotectin and NETs (r=0.34, p=0.002; r=0.29, p<0.01 respectively). Additionally, plasma samples from SSc patients with high levels of fMet induced de novo neutrophil activation through FPR1-dependent mechanisms. Our data for the first time implicates an important role for the mitochondrial component fMet in promoting neutrophil-mediated inflammation in SSc.</p>}},
author = {{Kuley, Runa and Stultz, Ryan D. and Duvvuri, Bhargavi and Wang, Ting and Fritzler, Marvin J. and Hesselstrand, Roger and Nelson, J. Lee and Lood, Christian}},
issn = {{1664-3224}},
keywords = {{autoimmunity; clinical biomarkers; mitochondrial peptides; neutrophil extracellular traps (NET); neutrophils (PMNs); systemic sclerosis}},
language = {{eng}},
publisher = {{Frontiers Media S. A.}},
series = {{Frontiers in Immunology}},
title = {{N-Formyl Methionine Peptide-Mediated Neutrophil Activation in Systemic Sclerosis}},
url = {{http://dx.doi.org/10.3389/fimmu.2021.785275}},
doi = {{10.3389/fimmu.2021.785275}},
volume = {{12}},
year = {{2022}},
}