Specific antibody protection of the extracellular cartilage matrix against collagen antibody-induced damage.
OBJECTIVE
The type II collagen (CII)-specific monoclonal antibodies (mAb) M2139 and CIIC1 induce arthritis in vivo and degrade bovine cartilage explants in vitro, whereas mAb CIIF4 is nonarthritogenic and prevents arthritis development when given in combination with M2139 and CIIC1. To determine the nature of the protective capacity of CIIF4 antibody, we examined the effects of adding CIIF4 to cartilage explants cultured in vitro with M2139 and CIIC1.


METHODS
Bovine cartilage explants were cultured in the presence of M2139 and CIIC1, with or without CIIF4. Histologic changes were examined, and chemical changes to collagens and proteoglycans were assessed by Fourier transform infrared microspectroscopy (FTIRM). Fresh cartilage and cartilage that had been freeze-thawed to kill chondrocytes cultured with or without the addition of GM6001, a broad-spectrum inhibitor of matrix metalloproteinases (MMPs), were compared using FTIRM analysis.


RESULTS
M2139 and CIIC1 caused progressive degradation of the cartilage surface and loss of CII, even in the absence of viable chondrocytes. CIIF4 did not cause cartilage damage, and when given with the arthritogenic mAb, it prevented their damage and permitted matrix regeneration, a process that required viable chondrocytes. Inhibition of MMP activity reduced cartilage damage but did not mimic the effects of CIIF4.


CONCLUSIONS
CII-reactive antibodies can cause cartilage damage or can be protective in vivo and in vitro, depending on their epitope specificity. Since CII antibodies of similar specificity also occur in rheumatoid arthritis in humans, more detailed studies should unravel the regulatory mechanisms operating at the effector level of arthritis pathogenesis.
Croxford
Allyson M
AM
Monash University, Clayton, Victoria, Australia.
Crombie
Duncan
D
McNaughton
Donald
D
Holmdahl
Rikard
R
Nandakumar
Kutty Selva
KS
Rowley
Merrill J
MJ
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002356:Cartilage / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D019902:Chondrocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D024043:Collagen Type II / Q000276:immunology*; D005109:Extracellular Matrix / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000276:immunology / Q000378:metabolism; D011509:Proteoglycans / Q000276:immunology / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D046509:Tissue Culture Techniques
D000911:Antibodies, Monoclonal; D024043:Collagen Type II; D011509:Proteoglycans; D020782:Matrix Metalloproteinases