Plasmin, the main molecule of the plasminogen activator system, is actually a broad-spectrum serine protease. Plasmin is vital for the degradation of fibrin as well as other elements of the extracellular matrix (ECM) in a variety of physiological and pathological processes. The purpose of this dissertation ended up being to elucidate the important roles of plasmin during pathological inflammation and infection in autoimmune and non-autoimmune diseases. For this reason, mouse models of rheumatoid arthritis (RA), bacterial arthritis, infection, and sepsis were used. Past reports from our laboratory have demonstrated that plasminogen-deficient mice are resilient to the development of collagen type II-induced arthritis (CIA).
Contents
INTRODUCTION
1. THE PLASMINOGEN ACTIVATOR (PA) SYSTEM
1.1. Plasminogen/plasmin
1.2. Plasminogen activators
1.2.1. Urokinase-type plasminogen activator (uPA)
1.2.2. Tissue-type plasminogen activator (tPA)
1.3. Inhibitors of the PA system
1.3.1. Plasminogen activator inhibitor type 1 (PAI-1)
1.3.2. Plasminogen activator inhibitor type 2 (PAI-2)
1.3.3. Protease nexin-1 (PN-1)
1.3.4. α2-antiplasmin (α2-AP)
2. STUDIES ON GENE-DEFICIENT MICE
2.1. Plasminogen-deficient mice
2.2. Human plasminogen abnormalities
2.3. tPA-deficient mice
2.4. uPA-deficient mice
2.5. tPA/uPA doubly deficient mice
2.6. PAI-1-deficient mice
2.7. PAI-2-deficient mice
3. INFLAMMATION
3.1. The roles of the plasminogen activator system in inflammation
3.2. Novel roles of the plasminogen activator system in signal transduction during inflammation
4. RHEUMATOID ARTHRITIS (RA)
4.1. Animal models of rheumatoid arthritis
4.2. Cytokines in rheumatoid arthritis
4.3. Roles of the plasminogen activator system in rheumatoid arthritis
5. INFECTION
5.1. The host defense against bacteria
5.2. Septic arthritis
5.3. Roles of the plasminogen activator system during infection and bacterial arthritis
6. SEPSIS
6.1. Cytokines and sepsis
6.2. Complement and sepsis
6.3. Coagulation and sepsis
6.4. Roles of the plasminogen activator system in sepsis
7. SUMMARY OF THE PRESENT STUDIES
7.1. Contrasting roles of plasminogen deficiency in different rheumatoid arthritis models (Paper I)
7.2. Protective effects of plasmin(ogen) in a mouse model of Staphylococcus aureus-induced arthritis (Paper II)
7.3. Beneficial and detrimental effects of plasmin(ogen) during infection and sepsis (Paper III)
CONCLUSIONS….
Source: Umea University
Download URL 2: Visit Now