|
|
||||||||||||||
|
|
|||||||||||||||
a The
Arthritis Research Institute, Department of Medicine, The University of
New South Wales, Australia, b The Garvan Institute of
Medical Research, c and Department of
Anatomical Pathology, St Vincent's Hospital, Sydney, Australia
Correspondence to: Dr K Scott, Department of Medicine, The University of New South Wales, St Vincent's Hospital, Level 9, Garvan Institute Building, 384 Victoria Street, Darlinghurst NSW 2010, Australia.
Accepted for publication 8 July 1998
OBJECTIVE
To determine the localisation and level
of expression of human type IIa secretory phospholipase A2
(sPLA2) in the synovium of rheumatoid arthritis (RA),
osteoarthritis (OA), and non-arthritic (NA) patients and to examine the
relation between sPLA2 and histological features of inflammation.
METHODS
Immunoperoxidase staining using the
anti-sPLA2 monoclonal antibody 9C1 was performed on frozen
sections of knee synovium of 10 RA, 10 OA, and 10 NA patients.
sPLA2 positive cells were scored on a scale of 0-3 in 10 fields of a representative tissue section from each case. Double
labelling imunofluorescence confocal microscopy with antibodies to CD14
or CD45 and 9C1 was used to determine cell type specificity.
Inflammation was assessed by semiquantitative scoring of lining layer
thickness and mononuclear cell infiltrates (MC) and a cumulative
inflammation score, generated by summing the two parameters. Scores in
each group were compared using non-parametric statistical analysis.
RESULTS
sPLA2 was localised to
endothelium (EC), vascular smooth muscle (VSM), and mast cells (M) in
all tissue sections. In RA and OA sections, staining was seen in both
macrophage-like and fibroblast-like cells in the synovial lining layer
(LL) and subsynovial lining layer (SLL). Perineural cells stained
positively. Subintimal lymphoid aggregates (LA) were negative in all
sections. The RA group showed significantly greater staining in
extravascular synovial tissue (median 3.6, range 1.5-6.0) than the
OA (median 1.95, range 0-5.3) or NA (median 0, range 0-5.9) groups
(p<0.05). LL staining was significantly higher in RA than both OA and
NA sections (p<0.05). The OA group showed a trend to higher staining
scores than the NA group that did not reach significance. There was a
significant correlation between the sPLA2 staining score
and inflammation score within the RA patient group (p<0.05).
CONCLUSIONS
The synovium is a site of increased
expression of sPLA2 antigen in both RA and OA relative to
NA. Its presence in both fibroblast and macrophage-like cells in the LL
and SLL of synovial tissue in RA and OA, but not NA, indicates that the
enzyme is specifically induced in these regions in both conditions with
expression in the LL being particularly characteristic of RA. The
widespread expression of sPLA2 in synovium suggests it is
likely to play a significant part in synovial pathology
This article has been cited by other articles:
![]() |
T. Ookoshi, K. Hasegawa, Y. Ohhashi, H. Kimura, N. Takahashi, H. Yoshida, R. Miyazaki, Y. Goto, and H. Naiki Lysophospholipids induce the nucleation and extension of {beta}2-microglobulin-related amyloid fibrils at a neutral pH Nephrol. Dial. Transplant., October 1, 2008; 23(10): 3247 - 3255. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Levick, D. Loch, B. Rolfe, R. C. Reid, D. P. Fairlie, S. M. Taylor, and L. Brown Antifibrotic Activity of an Inhibitor of Group IIA Secretory Phospholipase A2 in Young Spontaneously Hypertensive Rats. J. Immunol., June 1, 2006; 176(11): 7000 - 7007. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Moghaddami, M. Costabile, P. K. Grover, H. P. A. Jersmann, Z. H. Huang, C. S. T. Hii, and A. Ferrante Unique Effect of Arachidonic Acid on Human Neutrophil TNF Receptor Expression: Up-Regulation Involving Protein Kinase C, Extracellular Signal-Regulated Kinase, and Phospholipase A2 J. Immunol., September 1, 2003; 171(5): 2616 - 2624. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Hegen, L. Sun, N. Uozumi, K. Kume, M. E. Goad, C. L. Nickerson-Nutter, T. Shimizu, and J. D. Clark Cytosolic Phospholipase A2{alpha}-deficient Mice Are Resistant to Collagen-induced Arthritis J. Exp. Med., May 19, 2003; 197(10): 1297 - 1302. [Abstract] [Full Text] [PDF] |
||||
![]() |
D.-W. Park, J.-R. Kim, S.-Y. Kim, J.-K. Sonn, O.-S. Bang, S.-S. Kang, J.-H. Kim, and S.-H. Baek Akt as a Mediator of Secretory Phospholipase A2 Receptor-Involved Inducible Nitric Oxide Synthase Expression J. Immunol., February 15, 2003; 170(4): 2093 - 2099. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Chandra, J. Jasti, P. Kaur, S. Dey, M. Perbandt, A. Srinivasan, Ch. Betzel, and T. P. Singh Crystal Structure of a Complex Formed between a Snake Venom Phospholipase A2 and a Potent Peptide Inhibitor Phe-Leu-Ser-Tyr-Lys at 1.8 A Resolution J. Biol. Chem., October 18, 2002; 277(43): 41079 - 41085. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Murakami, K. Yoshihara, S. Shimbara, G. Lambeau, M. H. Gelb, A. G. Singer, M. Sawada, N. Inagaki, H. Nagai, M. Ishihara, et al. Cellular Arachidonate-releasing Function and Inflammation-associated Expression of Group IIF Secretory Phospholipase A2 J. Biol. Chem., May 17, 2002; 277(21): 19145 - 19155. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Nijmeijer, W. K Lagrand, A. Baidoshvili, Y. T.P Lubbers, W. T. Hermens, C. J.L.M Meijer, C. A Visser, C.E. Hack, and H. W.M Niessen Secretory type II phospholipase A2 binds to ischemic myocardium during myocardial infarction in humans Cardiovasc Res, January 1, 2002; 53(1): 138 - 146. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Bidgood, O. S. Jamal, A. M. Cunningham, P. M. Brooks, and K. F. Scott Type IIA Secretory Phospholipase A2 Up-Regulates Cyclooxygenase-2 and Amplifies Cytokine-Mediated Prostaglandin Production in Human Rheumatoid Synoviocytes J. Immunol., September 1, 2000; 165(5): 2790 - 2797. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. B. Church, A. S. Inglis, A. Tseng, R. Duell, P.-W. Lei, K. J. Bryant, and K. F. Scott A Novel Approach to the Design of Inhibitors of Human Secreted Phospholipase A2 Based on Native Peptide Inhibition J. Biol. Chem., August 24, 2001; 276(35): 33156 - 33164. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |