Secretion of oncostatin M by neutrophils in rheumatoid arthritis.
OBJECTIVE
Neutrophils are known to express and release a large number of proinflammatory cytokines when they are stimulated by inflammatory stimuli. The objective of this study was to determine whether neutrophils express oncostatin M (OSM), a member of the interleukin-6 family of cytokines that has been implicated in the pathogenesis of inflammatory joint disease.


METHODS
Neutrophils were isolated from the blood of healthy volunteer donors and from the blood and synovial fluid of patients with rheumatoid arthritis (RA). OSM levels were measured in cell extracts and in culture supernatants by Western blotting. Total RNA was isolated from control and granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated neutrophils, and OSM messenger RNA levels were quantified by hybridization of a radiolabeled probe.


RESULTS
GM-CSF stimulated a rapid and transient expression and release of OSM from blood neutrophils, which was more rapid than the expression and release from blood monocytes. A 28-kd protein was identified in cell extracts, but an additional 25-kd isoform was detected in culture supernatants. Synovial fluid neutrophils could not be stimulated to express OSM, but this cytokine was detected in cell-free supernatants at various levels.


CONCLUSIONS
Blood neutrophils can be stimulated to express and rapidly release large quantities of OSM. We propose that this important cytokine is released from neutrophils as they infiltrate rheumatoid joints and, thus, contribute to the complex cytokine network that characterizes RA.
Cross
Andrew
A
Academic Rheumatology Unit, University of Liverpool, University Hospital Aintree, Longmoor Lane, Liverpool L9 7AL, UK.
Edwards
Steven W
SW
Bucknall
Roger C
RC
Moots
Robert J
RJ
D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D053683:Oncostatin M; D010455:Peptides / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013582:Synovial Fluid / Q000378:metabolism
C508351:OSM protein, human; D010455:Peptides; D012333:RNA, Messenger; D053683:Oncostatin M; D016178:Granulocyte-Macrophage Colony-Stimulating Factor