Table 1.
Studies of intrinsic and contact system factors: effects on neuroinflammatory processes in transgenic mice or using pharmacological substances.
| Mouse line or treatment | Model (peptide) | Genetic background | Effects in models of autoimmune neurodegeneration | Reference |
|---|---|---|---|---|
| B1R−/− | Active EAE (MOG) | C57BL/6 | Delayed EAE onset, reduced clinical deficits, reduced inflammation and demyelination, decreased expression of endothelial adhesion molecules, reduced migration of lymphocytes | (25) |
| Earlier EAE onset, severe clinical disease course with enhanced inflammation, demyelination, glial activation, increased migration of CD4+ T cells, especially TH17 cells | (26) | |||
| Delayed EAE onset, reduced clinical deficits, reduced inflammation and demyelination, decreased cytokine production of CD4+ T cells | (27) | |||
| Delayed EAE onset, reduced clinical deficits, reduced glial activation, decreased release of proinflammatory mediators by astrocytes | (28) | |||
| Des-Arg9-BK (B1R activator) | Active EAE (MOG) | C57BL/6 | No clinical effect | (27) |
| R838 (B1R agonist) | Active EAE (MOG) | C57BL/6 | Aggravated disease course, enhanced inflammation, demyelination, axonal damage | (25) |
| Milder clinical deficits | (26) | |||
| Active RR-EAE (PLP) | SJL | Reduced clinical deficits | (26) | |
| Des-Arg9-[Leu8]-BK (B1R inhibitor) | Active EAE (MOG) | C57BL/6 | Delayed EAE onset, reduced clinical deficits, decreased release of proinflammatory mediators by astrocytes | (28) |
| Delayed EAE onset, reduced clinical deficits, reduced inflammation and demyelination, decreased cytokine production of CD4+ T cells | (27) | |||
| R715 (B1R inhibitor) | Active EAE (MOG) | C57BL/6 | Reduced clinical deficits, reduced inflammation, demyelination, axonal damage | (25) |
| Accelerated disease onset | (26) | |||
| B2R−/− | Active EAE (MOG) | C57BL/6 | No effect on clinical course, immune cells, cytokine production | (25, 26) |
| Moderate reduced clinical deficits, reduced inflammation, reduced leukocyte adhesion, decreased chemokine (CCL2, CCL5) production | (29) | |||
| HOE-140 (B2R inhibitor) | Active EAE (MOG) | C57BL/6 | Moderate or no effect on clinical disease course, immune cells, cytokine production | (25–28) |
| Moderate reduced clinical deficits, reduced inflammation, reduced leukocyte adhesion, decreased chemokine (CCL2, CCL5) production | (29) | |||
| F12−/− | Active EAE (MOG) | C57BL/6 | Delayed EAE onset, reduced clinical deficits, reduced inflammation and demyelination, reduced TH17 cells, decreased cytokine production (IL-6, IL-23) of DC | (15) |
| rHA-Infestin 4 (FXIIa inhibitor) | Active EAE (MOG) | C57BL/6 | Delayed EAE onset, reduced clinical deficits, reduced inflammation and demyelination, reduced cytokine production (IL-6, IL-17A) | (15) |
| Active EAE (PLP) | SJL | Ameliorated disease course | (15) | |
| F11−/− | Active EAE (MOG) | C57BL/6 | No effect on clinical symptoms, inflammation and demyelination | (15) |
| C1q−/− | Active EAE (MOG) | C57BL/6 | No effect on clinical symptoms | (30) |
| C3−/− | Active EAE (MOG) | 129SVJ/C57BL/6 | Reduced clinical deficits, decreased inflammation and demyelination | (31) |
| No clinical effect, but higher mortality, tendency to enhanced inflammation and demyelination | (32) | |||
| C3−/− | Active + AT-EAE (MOG) | C57BL/6 | Reduced clinical deficits, reduced infiltration of T cells | (33, 34) |
| C5−/− | Active EAE (guinea pig myelin) | B10.D2/oSnJ | Moderate reduction of clinical deficits, narrow zones of inflammation and demyelination, gliosis, reduced remyelination, enhanced apoptosis of oligodendrocytes, axonal damage | (35, 36) |
| C5a/GFAP | Active EAE (MOG) | C57BL/6 | No clinical effect | (37) |
| Cd87−/− | Active EAE (MOG) | C57BL/6 | Aggravated disease course, enhanced inflammation, axonal damage, reduced T-cell proliferation and cytokine production | (38) |
| Delayed disease onset, reduced clinical deficits, reduced inflammation, enhanced demyelination and axonal damage | (39) | |||
| Active EAE (MOG) in BM-chimera | Reduced clinical deficits with Cd87−/− BM, partial protection of Cd87−/− hosts | (15) | ||
AT, adoptive transfer; B1R, bradykinin receptor 1; B2R, bradykinin receptor 2; BK, bradykinin; BM, bone marrow; CCL, chemokine (C–C) motif ligand; DC, dendritic cells; EAE; experimental autoimmune encephalomyelitis; FXIIa, activated factor XII; IL, interleukin; MOG, myelin oligodendrocyte glycoprotein; PLP, proteolipid protein; rHA, recombinant human albumin; RR, relapsing–remitting; TH17, IL-17A-producing effector T helper cells.