Elevated levels of 92-kd type IV collagenase (matrix metalloproteinase 9) in giant cell arteritis.
OBJECTIVE
To determine if circulating gelatinase activity and matrix metalloproteinase 9 (MMP-9) (gelatinase B, or 92-kd type IV collagenase) antigenic levels are elevated in sera of patients with giant cell arteritis (GCA), and to ascertain if MMP-9 messenger RNA (mRNA) is deposited in situ at sites of disease involvement.


METHODS
Serum samples were collected from 12 patients with GCA and 12 healthy volunteers. Vascular tissue was obtained at the time of temporal artery biopsy. Type IV collagenase activity was determined by gelatin substrate zymography and the quantitative biotinylated gelatin substrate degradation assay. A double-sandwich immunoassay utilizing 2 different isotypes of monoclonal antibodies generated against MMP-9 was used for measuring serum MMP-9 antigenic levels. Finally, to localize sites of MMP-9 mRNA transcription in inflamed arteries, the method of reverse transcriptase in situ polymerase chain reaction (RTisPCR) was utilized.


RESULTS
Serum gelatinase activity and MMP-9 titers were significantly increased in patients with GCA (mean +/- SEM 198.9 +/- 36.9 micrograms gelatin/hour/ml serum, versus 21.2 +/- 4.0 in controls; P = 0.0006). The differences in antigenic MMP-9 levels were even more prominent (3005.4 +/- 900.6 ng/ml and 31.6 +/- 9.8 ng/ml in GCA and control sera, respectively; P = 0.007). By RTisPCR, MMP-9 mRNA was mainly detected in cytoplasm of cells resembling smooth muscle cells and fibroblasts in regions of fragmented elastic tissue in the lamina media.


CONCLUSIONS
Gelatinase activity, and specifically MMP-9 levels, are substantially elevated in sera of patients with GCA. Detection of MMP-9 mRNA in the lamina media of inflamed vasculature suggests that degradation of intercellular matrix, particularly elastic fibers, may play a key role in the pathogenesis of GCA. Further studies are needed to determine if the circulating MMP-9 level could be utilized as a clinical marker of disease activity.
Sorbi
D
D
Northport VA Medical Center, New York, USA.
French
D L
DL
Nuovo
G J
GJ
Kew
R R
RR
Arbeit
L A
LA
Gruber
B L
BL
D015415:Biomarkers; D001710:Biotin; D017364:Collagenases / Q000097:blood* / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005780:Gelatin / Q000378:metabolism; D013700:Giant Cell Arteritis / Q000097:blood* / Q000201:enzymology; D006801:Humans; D017403:In Situ Hybridization; D020780:Matrix Metalloproteinase 9; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic / Q000502:physiology
D015415:Biomarkers; D012333:RNA, Messenger; D001710:Biotin; D005780:Gelatin; D017364:Collagenases; D020780:Matrix Metalloproteinase 9