Myeloid-related proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticular-onset juvenile rheumatoid arthritis.
OBJECTIVE
To analyze which physiologic stimuli induce secretion of myeloid-related protein 8 (MRP8) and MRP14, two S100 proteins expressed in neutrophils and monocytes, and to determine whether serum concentrations of these proteins are reliable parameters for monitoring inflammatory activity in pauciarticular juvenile rheumatoid arthritis (JRA).


METHODS
Secretion of MRP8 and MRP14 was analyzed using a coculture system of endothelial cells and monocytes. Concentrations of MRP8/MRP14 in the serum and synovial fluid of JRA patients or culture medium were determined by enzyme-linked immunosorbent assay. The expression of MRP8 and MRP14 by leukocytes in synovial tissue or fluid was investigated using immunohistochemistry.


RESULTS
MRP8 and MRP14 were specifically released during interaction of activated monocytes with tumor necrosis factor-stimulated endothelial cells. Secretion was mediated via an increase in intracellular calcium levels in monocytes. In contrast, contact with resting endothelium inhibited protein kinase C-induced secretion of the proteins by monocytes. In JRA patients, MRP8 and MRP14 were strongly expressed in infiltrating neutrophils and monocytes within the inflamed joints and could be found in significantly higher concentrations in synovial fluid (mean 42,800 ng/ml) compared with serum (2,060 ng/ml). Concentrations of MRP8/MRP14 in serum correlated well with those in synovial fluid (r = 0.78) and showed a strong correlation with disease activity (r = 0.62). After intraarticular triamcinolone therapy, the serum concentrations of MRP8/MRP14 decreased significantly in therapy responders, whereas no differences were found in patients who showed no clinical benefit.


CONCLUSIONS
MRP8 and MRP14 are specifically released during the interaction of monocytes with inflammatory activated endothelium, probably at sites of local inflammation. Their serum concentrations represent a useful marker for monitoring local inflammation in JRA.
Frosch
M
M
University of Münster, Germany.
Strey
A
A
Vogl
T
T
Wulffraat
N M
NM
Kuis
W
W
Sunderkötter
C
C
Harms
E
E
Sorg
C
C
Roth
J
J
D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000943:Antigens, Differentiation / Q000097:blood / Q000378:metabolism*; D001171:Arthritis, Juvenile / Q000097:blood* / Q000188:drug therapy; D002135:Calcium-Binding Proteins / Q000097:blood / Q000378:metabolism*; D040501:Calgranulin A; D040502:Calgranulin B; D002450:Cell Communication / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004727:Endothelium / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D010586:Phagocytes / Q000166:cytology*; D009418:S100 Proteins / Q000097:blood / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000943:Antigens, Differentiation; D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D040502:Calgranulin B; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D009418:S100 Proteins; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D019284:Thapsigargin