Properdin Regulation of Complement Activation Affects Colitis in Interleukin 10 Gene-Deficient Mice
Jain, U; Midgen, CA; Schwaeble, WJ; Stover, CM; Stadnyk, AW
| HERO ID | 2902154 |
|---|---|
| In Press | No |
| Year | 2015 |
| Title | Properdin Regulation of Complement Activation Affects Colitis in Interleukin 10 Gene-Deficient Mice |
| Authors | Jain, U; Midgen, CA; Schwaeble, WJ; Stover, CM; Stadnyk, AW |
| Journal | Inflammatory Bowel Diseases |
| Volume | 21 |
| Issue | 7 |
| Page Numbers | 1519-1528 |
| Abstract | <strong>BACKGROUND: </strong>Interleukin 10-deficient mice (IL-10) are a popular model used to dissect the mechanisms underlying inflammatory bowel diseases. The role of complement, a host defense mechanism that bridges the innate and adaptive immune systems, has not been described in this model. We therefore studied the effect of deficiency of properdin, a positive regulator of complement, on colitis in mice with the IL-10 background.<br /><br /><strong>METHODS: </strong>For acute colitis, IL-10 and IL-10/properdin double knockout (DKO) or radiation bone marrow-reconstituted chimeric mice, had piroxicam added to their powdered chow for 14 days. For chronic colitis, 2.5% dextran sodium sulfate was added to the animals' water for 4 days then the mice were killed 8 weeks later. Colons were assessed for inflammation, cell infiltration, and cytokine and complement measurements. Bacterial translocation was measured by cultivating bacteria from organs on Luria broth agar plates.<br /><br /><strong>RESULTS: </strong>C3a and C5a levels and C9 deposition were all increased in piroxicam-fed IL-10 mice compared with mice not fed piroxicam. Piroxicam-fed DKO mice lacked increased C5a and C9 deposition combined with exacerbated colitis, reduced numbers of infiltrating neutrophils, and markedly higher local and systemic bacterial numbers compared with IL-10 mice. Bone marrow cells from IL-10 mice were sufficient to restore protection against the heightened colitis in piroxicam-fed DKO mice.<br /><br /><strong>CONCLUSIONS: </strong>Complement is activated in the IL-10 mouse mucosa in a properdin-dependent manner. In the absence of terminal complement activation, the inflammation is heightened, likely due to a lack of neutrophil control over microbes escaping from the intestines. |
| Doi | 10.1097/MIB.0000000000000398 |
| Pmid | 25939041 |
| Wosid | WOS:000356602200005 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | complement; neutrophils; properdin; C5a; IL-10 |