Table 2.
In vivo immunoregulatory properties of the C5a/C5aR system.
| Model | Treatment | Outcomes | References |
|---|---|---|---|
| E. coli-induced sepsis | C5a neutralizing antibody | Increased survival rate, decreased lung edema and oxygenation | Stevens et al., 1986; Hangen et al., 1987 |
| anti-C5a antibody | Decreased IL-6 level in serum | Hopken et al., 1996 | |
| C5aR knockout | Attenuation of NK and NKT cell activation | Fusakio et al., 2011 | |
| Reduced TNF-alpha and IFN-gamma release by NK and NKT cells | |||
| Impaired recruitment of NK and NKT cells to the site of infection | |||
| Increased survival rate | |||
| LPS-induced endotoxic shock | C5a neutralizing antibody | Attenuated septic parameters | Smedegard et al., 1989 |
| C5aR knockout | Increased circulating IL-23 and IL-17A level | Van Epps et al., 1990; Bosmann et al., 2012 | |
| Increased resistance to endotoxic shock | |||
| C5L2 knockout | Increased serum IL-1beta while decreased survival rate | Han et al., 2011 | |
| CLP-induced sepsis | anti-C5a antibody | Reduced bacterial colony forming-units while improved respiratory burst | Czermak et al., 1999; Laudes et al., 2002b; Guo et al., 2003, 2006; Flierl et al., 2008a, 2009; Atefi et al., 2011; Bosmann et al., 2011a |
| Reduced IL-17F level in serum | |||
| Attenuated coagulant paremeters | |||
| Reduced apoptosis of adrenal medulla cell | |||
| Ameliorated septic encephalopathy | |||
| Restoration of neutrophil to spontaneous apoptosis Reduced inflammatory mediators' production by cardiomyocytes while attenuation of cardiac dysfunction | |||
| Restoration of C5aR content on neutrophils | |||
| C5aR knockout | Decreased plasma levels of IL-1beta, IL-6, MIP-2, and MIP-1alpha while increased survival rate | Rittirsch et al., 2008 | |
| C5aR antagonist | Improved survival | Huber-Lang et al., 2002a | |
| C5aR antibody | Reduced IL-6 and TNF-alpha production in serum, and bacterial burden while improved survival | Zahedi et al., 2000 | |
| anti-C5L2 antibody | Increased serum IL-6 level | ||
| C5L2 knockout | Decreased serum levels of IL-1beta, MIP-2, MIP-1alpha, and HMGB1 while improved survival | Rittirsch et al., 2008; Atefi et al., 2011 | |
| Increased pro-inflammatory mediators' production from cardiomyocytes | |||
| House dust mite-induced allergic asthma | C5/C5aR knockout | Increased IL-23 production by dendritic cells and Th17 cell differentiation and proliferation | Lajoie et al., 2010 |
| Enhanced airway hyperresponsiveness | |||
| C5L2 knockout | Attenuated asthmatic phenotye | Johswich et al., 2006 | |
| IgG IC-induced acute lung injury | C5L2 knockout | Reduced lung inflammation | Gerard et al., 2005 |