Table 3.
Studies of coagulation system factors: effects on inflammatory processes using transgenic mice or pharmacological substances.
| Mouse line or treatment | Model (peptide) | Genetic background or species | Effect in arthritis and colitis models | Reference |
|---|---|---|---|---|
| B1R/B2R−/− | CAIA (anti-CII antibodies) | C57BL/6 | Decreased clinical symptoms, reduced inflammation and cytokine levels | (83) |
| C11C1 (HMWK antibody) | Reactive arthritis (PG-PS) | Lewis rats | Reduced joint diameter, local inflammation | (84) |
| Spontaneous arthritis | HLA-B27 transgenic rats | Reduced joint destruction, inflammation | (85) | |
| Fib−/− | CIA (type II collagen) | DBA/1J | Reduced incidence, severity, joint destruction, synovial inflammation | (53) |
| Fib−/− | Colitis-associated cancer (DSS) | C57BL/6 | Reduced inflammation-driven adenoma formation | (54) |
| FibΔ5 | CIA (type II collagen) | DBA/1J | No effect on incidence and severity | (53) |
| Fibγ390–396A | CIA (type II collagen) | DBA/1J | Reduced incidence, severity, joint destruction, synovial inflammation | (53) |
| Fibγ390–396A | Colitis (DSS) | C57BL/6 | Diminished inflammatory disease, reduced ulceration, cytokine levels and neutrophil infiltration | (54) |
| Fibγ390–396A | Colitis-associated cancer (DSS) | C57BL/6 | Reduced inflammation-driven adenoma formation | (54) |
| Heparin | CIA (type II collagen) | DBA/1 | No effect on clinical score | (82) |
| Hirudin | AIA (mBSA) | C57BL/6 | Reduced knee joint inflammation, fibrin deposition | (80) |
| CIA (type II collagen) | DBA/1J | Decreased disease incidence, severity, reduced loss of articular cartilage, inflammation, fibrin deposition and PAR-1 expression | (81) | |
| HMWK−/− | Reactive arthritis (PG-PS) | Rats | No clinical signs of arthritis, absence of inflammation | (86) |
| MEN16132 (B2R antagonist) | Inflammatory arthritis (carrageenan) | Rats | Reduced knee diameter and myeloperoxidase activity | (87) |
| P8720 (PK inhibitor) | Reactive arthritis (PG-PS) | Lewis rats | Decreased joint swelling, reduced inflammation | (88) |
| PKSI-527 (PK inhibitor) | CIA (type II collagen) | DBA/1 | Reduced severity of arthritis, reduced PK and HMWK plasma levels | (89) |
| Plg−/− | AIA (mBSA) | C57BL/6 | Enhanced inflammation, bone erosion, synovial thickness, fibrin deposition | (90) |
| Plg−/− | CIA (type II collagen) | C57BL/6xDBA/1 | No clinical symptoms of disease, no signs of inflammation | (91) |
| CAIA (anti-CII antibodies) | No clinical symptoms of disease, no signs of inflammation | (91) | ||
| AIA (mBSA) | Enhanced synovial thickness | (92) | ||
| CIA (type II collagen) | Reduced synovial thickness | (92) | ||
| Tg197Fib−/− | TNF-transgenic model, spontaneous polyarthritis | No effect on incidence, severity, inflammation, joint destruction | (53) | |
| uPA | CIA (type II collagen) | DBA/1 | No effect on clinical score, reduced fibrin deposits in joints, decreased plasma d-dimer level | (82) |
| uPA−/− | AIA (mBSA) | Ola129xC57BL/6 | Enhanced joint inflammation, bone erosion, synovial thickness, fibrin deposition | (90) |
| uPA−/− | Monoarticular arthritis (mBSA/IL-1) | C57BL/6 | Enhanced arthritis, fibrin deposition, increased numbers of macrophages | (93) |
| CIA (type II collagen) | Reduced clinical symptoms, decreased inflammation, cartilage destruction, bone erosion, reduced cytokine production | (94) | ||
| CAIA (M2139, CIIC1 antibodies) | No clinical signs of disease | (95) | ||
| AIA (mBSA) | Enhanced proteoglycan loss, inflammation, bone erosion | (92, 96) | ||
| uPA−/− | CIA (type II collagen) | C57BL/6xDBA/1 | Reduced clinical symptoms, no histological changes | (91) |
| K/BxN serum transfer arthritis (K/BxN serum) | No clinical signs of disease, reduced inflammation, bone erosion, fibrin deposition | (95, 96) | ||
| tPA | CIA (type II collagen) | DBA/1 | No effect on clinical score, reduced fibrin deposits in joints | (82) |
| tPA−/− | Monoarticular arthritis (mBSA/IL-1) | C57BL/6 | Enhanced arthritis, fibrin deposition, increased numbers of macrophages | (93) |
| CIA (type II collagen) | Aggravated clinical symptoms, enhanced inflammation, cartilage destruction, bone erosion, fibrin deposition | (94) | ||
AIA, antigen-induced arthritis; B1R, bradykinin receptor I; B2R, bradykinin receptor 2; CAIA, type II collagen mAb-induced arthritis; CIA, collagen-induced arthritis; CII, collagen type II; DSS, dextran sulfate sodium; HLA, human leukocyte antigen; HMWK, high molecular weight kininogen; mBSA, methylated bovine serum albumin; PAR-1, protease-activated receptor; PG-PS, peptidoglycan-polysaccharide; PK, plasma kallikrein; TNF, tumor necrosis factor; tPA, tissue plasminogen activator; uPA, urokinase plasminogen activator.