Clinical and histopathological characterization of a large animal (ovine) model of collagen-induced arthritis

Abdalmula, Anwar; Washington, Elizabeth A.; House, Jacqueline V.; Dooley, Laura; Blacklaws, Barbara; Ghosh, Peter; Bailey, S. R.; Kimpton, Wayne G.

doi:10.1016/j.vetimm.2014.03.007

Cited by 17 publications

(22 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is not the case with native α10β1 where the electropositive R215 will repel GROGER. This α10 residue is conserved in many other species; rat or mouse [29], dog [30] and sheep [31], animals that are frequently used in models of experimental arthritis; cow, a large-scale source of cartilage [32]; and zebrafish [33], [34], [35], a widely-used developmental model. All contain this critical arginine residue.…”

Section: Discussionmentioning

confidence: 99%

Unique charge-dependent constraint on collagen recognition by integrin α10β1

et al. 2017

View full text Add to dashboard Cite

The collagen-binding integrins recognise collagen through their inserted (I) domain, where co-ordination of a Mg2 + ion in the metal ion-dependent site is reorganised by ligation by a collagen glutamate residue found in specific collagen hexapeptide motifs. Here we show that GROGER, found in the N-terminal domain of collagens I and III, is only weakly recognised by α10β1, an important collagen receptor on chondrocytes, contrasting with the other collagen-binding integrins. Alignment of I domain sequence and molecular modelling revealed a clash between a unique arginine residue (R215) in α10β1 and the positively-charged GROGER. Replacement of R215 with glutamine restored binding. Substituting arginine at the equivalent locus (Q214) in integrins α1 and α2 I domains impaired their binding to GROGER. Collagen II, abundant in cartilage, lacks GROGER. GRSGET is uniquely expressed in the C-terminus of collagen II, but this motif is similarly not recognised by α10β1. These data suggest an evolutionary imperative to maintain accessibility of the terminal domains of collagen II in tissues such as cartilage, perhaps during endochondral ossification, where α10β1 is the main collagen-binding integrin.

show abstract

Section: Discussionmentioning

confidence: 99%

Unique charge-dependent constraint on collagen recognition by integrin α10β1

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Blood was centrifuged at 3,000 g at 4°C for 10 min and plasma was aliquoted and frozen at -80°C. Quantification of interleukin 6 (IL-6) and interleukin 10 (IL-10) levels were performed using in-house enzyme-linked immunosorbent assays (ELISA), as previously described [ 13 ]. Tumour necrosis factor alpha (TNF-α) was measured using a commercially available ELISA kit (Kingfisher Biotech Inc., MN, USA).…”

Section: Methodsmentioning

confidence: 99%

Effects of selective β1-adrenoceptor blockade on cardiovascular and renal function and circulating cytokines in ovine hyperdynamic sepsis

et al. 2014

View full text Add to dashboard Cite

IntroductionActivation of the sympathetic nervous system has beneficial cardiovascular effects in sepsis, but there is also evidence that sympatholytics have beneficial actions in sepsis. We therefore determined the effect of selective β1-adrenoceptor blockade on cardiac and renal function and cytokine release in ovine hyperdynamic sepsis.MethodsHyperdynamic sepsis was induced by infusion of live E. coli for 24 hours in nine conscious sheep instrumented with flow probes on the pulmonary and left renal artery. Cardiovascular and renal function and levels of plasma cytokines were determined in a control group and during selective β1-adrenoceptor blockade with atenolol (10 mg intravenous bolus then 0.125 mg/kg/h) from 8 to 24 hours of sepsis.ResultsHyperdynamic sepsis was characterized by hypotension with increases in cardiac output (CO), heart rate (HR) and renal blood flow (RBF), and acute kidney injury. Atenolol caused sustained reductions in HR (P <0.001) and CO (P <0.001). Despite the lower CO the sepsis-induced fall in mean arterial pressure (MAP) was similar in both groups. The sepsis-induced increase in RBF, decrease in renal function and increase in arterial lactate were unaffected by atenolol. Sepsis increased plasma levels of tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and IL-10. Atenolol caused a further increase in IL-10, but did not affect levels of TNF-α or IL-6.ConclusionsIn sepsis, selective β1-adrenoceptor blockade reduced CO, but not MAP. During sepsis, atenolol did not alter the development of acute kidney injury or the levels of pro-inflammatory cytokines, but enhanced the release of IL-10. Atenolol appears safe in sepsis, has no deleterious cardiovascular or renal effects, and has an anti-inflammatory effect.

show abstract

“…Collagen-induced arthritis (CIA), an established experimental animal model of arthritis with many histopathological features that are similar to human RA, was established to study the metabolic profiles and differential metabolites (Abdalmula et al, 2014). By analyzing metabolic profiling using LC-MS in the serum of CIA rats and control rats, ten metabolites were identified associated with the pathogenesis of CIA (Ding et al, 2014).…”

Section: Application Of Metabolomics In Rheumatoid Arthritismentioning

confidence: 99%