Journal
MODERN RHEUMATOLOGY
Volume 30, Issue 2, Pages 345-349Publisher
OXFORD UNIV PRESS
DOI: 10.1080/14397595.2019.1583819
Keywords
Anti-carbamylated protein antibodies; anti-modified protein antibodies; autoantibodies; neutrophils; rheumatoid arthritis
Categories
Funding
- Mitsubishi Tanabe Pharma Co.
- Chugai Pharmaceutical Co., Ltd.
- UCB Japan Co., Ltd.
- AYUMI Pharmaceutical Co.
- Astellas
- Bristol-Myers Squibb
Ask authors/readers for more resources
Objective: An anti-carbamylated albumin antibody was detected in rheumatoid arthritis (RA) patients, and its presence was associated with serum myeloperoxidase (MPO) levels, as we reported previously. Since MPO is a key enzyme for carbamylation and is released by neutrophil extracellular traps (NETs), we aimed to demonstrate that NETosis induces carbamylation. Methods: Human neutrophils were isolated from a healthy donor, pre-treated with or without diphenyleneiodonium (DPI, an inhibitor for the generation of reactive oxygen species (ROS)), Cl-amidine (a peptidylarginine deiminase inhibitor), 4-aminobenzoic acid hydrazide (4-ABAH, an MPO inhibitor), or GW311616A (a neutrophil elastase (NE) inhibitor), and incubated for 8 h with or without phorbol 12-myristate 13-acetate (PMA). Proteins in the medium were collected and the carbamylation of albumin was evaluated by Western blotting. Results: The carbamylation of albumin was detected in the culture medium of activated neutrophils. NETosis was observed under the stimulation by PMA. DPI and 4-ABAH inhibited the carbamylation of albumin and NETosis. GW311616A inhibited NETosis, but not carbamylation. Neither carbamylation nor NETosis was inhibited by Cl-amidine. Conclusion: Activated neutrophils may carbamylate ambient albumin, and this is dependent on ROS and MPO, but does not require NETosis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available