Effect of anti‐macrophage inflammatory protein‐1α on leukocyte trafficking and disease progression in experimental autoimmune uveoretinitis

Crane, Isabel J.; Xu, Heping; Manivannan, A.; McKillop-Smith, Susan; Lamont, Graeme R.; Wallace, Carol A.; Liversidge, Janet; Sharp, P.; Forrester, John V.

doi:10.1002/immu.200310014

Cited by 27 publications

(16 citation statements)

References 30 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3 In vivo monocyte trafficking was studied using our scanning laser ophthalmoscopy (SLO) technique as described. 22,23 This nonsurgical technique minimizes any leukocyte trafficking artifacts. The retinal vasculature is imaged through the intact cornea, and adoptively transferred leukocytes may be tracked as they enter through the retinal artery, traverse the capillary network, and exit through the retinal vein.…”

Section: Methodsmentioning

confidence: 99%

Critical but divergent roles for CD62L and CD44 in directing blood monocyte trafficking in vivo during inflammation

Manivannan

Crane

et al. 2008

Blood

Self Cite

View full text Add to dashboard Cite

Using noninvasive in vivo imaging and experimental autoimmune uveoretinitis as a model, we show for the first time that the mechanisms controlling blood monocyte recirculation through peripheral and lymphoid tissues alter during inflammation. The recirculation of monocytes in mice with ocular inflammation but not controls was found to depend on the selectin CD62-ligand (CD62L) and on CD44. Not only was rolling efficiency ablated or markedly reduced in antibody-treated mice, but most of the labeled monocytes also disappeared from the circulation within seconds, anti-CD44–treated monocytes homing to the lymph nodes and anti–CD62L-treated monocytes homing to the spleen. Our data indicate that, although PSGL-1 has a partial role in the transmigration of monocytes into the inflamed retina, CD62L has a key role in regulating recruitment of monocytes to lymphoid tissue from the blood during inflammation and that CD44 is required to maintain CD62L+ inflammatory monocytes within the circulation during inflammation. This effect was systemic, because sequestered monocytes accumulated in mesenteric as well as draining cervical lymph nodes, and inflammation dependent, because depletion of circulating blood monocytes was much reduced or absent in normal mice and accumulations of adoptively transferred monocytes in the lymphoid tissues did not occur.

show abstract

Section: Methodsmentioning

confidence: 99%

Critical but divergent roles for CD62L and CD44 in directing blood monocyte trafficking in vivo during inflammation

Manivannan

Crane

et al. 2008

Blood

Self Cite

View full text Add to dashboard Cite

show abstract

“…MIP-1a mRNA, on the other hand, was not expressed at any of the time points studied. It has, however, been reported that MIP-1a is of major importance in the recruitment of leukocytes into the ocular lesions in EAU [22]. A possible explanation of these conflicting results could be the different type of disease manifestation in the mouse and rat EAU models.…”

Section: Studies On Animalsmentioning

confidence: 87%

The role of chemokines and their receptors in uveitis

et al. 2007

View full text Add to dashboard Cite

T-cell-dependent immunological events are increasingly being regarded as extremely important in the pathogenesis of uveitis. Several studies have also shown that macrophages are major effectors of tissue damage in uveitis. Neutrophils are also thought to play a central role in the pathogenesis of Behçet's disease. Chemokines are a superfamily of 8 to 10-kDa secreted proteins that direct the recruitment of leukocytes to sites of inflammation. The specific biological effects of chemokines are mediated by a family of seven transmembrane-spanning G-protein-coupled receptors. Recent studies of animals and humans suggest that chemokines and their receptors play a key role in leukocyte recruitment into the eye in uveitis. A strategy for blocking chemokines or chemokine receptors could be a new approach for treatment of uveitis.

show abstract

“…15 These chemokines can be produced by T cells following T-cell receptor engagement or after nonspecific activation 16 and have been implicated in a range of inflammatory conditions 17,18 including those with an autoimmune basis. 19,20 However, T cells from some normal donors may also produce CCL3 and CCL4 constitutively, and T-cell clones have been established from normal donors that produce substantial levels of CCL3 and CCL4. 21 It is not known whether this spontaneous production is due to inherent genetic factors or whether it has an environmental basis.…”

Section: Resultsmentioning

confidence: 99%

“…We have shown that treatment with neutralizing antibody to CCL3 can reduce the severity of experimental autoimmune uveitis, an animal model of PII. 20 Regulation of CCL3 and CCL4 production by T cells infiltrating the retina is important to protect the retina from an inflammatory response, and the RPE cells are likely to be key to this regulation.…”

Section: Resultsmentioning

confidence: 99%

Regulation of T-Lymphocyte CCL3 and CCL4 Production by Retinal Pigment Epithelial Cells

Wallace

Moir

Malone

et al. 2013

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PURPOSE.Retinal pigment epithelial (RPE) cells have an important role in the immune suppression associated with the immune privilege of the eye. Some aspects of this remain unclear and this study aimed to determine how RPE cells could influence the production of chemokines by T lymphocytes.METHODS. T lymphocytes, separated from peripheral blood of normal volunteers, and RPE cells, cultured from donor eyes, were cultured separately and together, either in contact or in transwells. Supernatants were analyzed for CCL3, CCL4, and soluble CD54 (sCD54) by ELISA. Blocking agents were used to determine which soluble mediators were involved. RESULTS.Coculture of RPE cells with activated lymphocytes resulted in a reduction in CCL3 and CCL4 production by lymphocytes, primarily by soluble mediators. Soluble CD54 was markedly increased on coculture of lymphocytes with RPE cells. Soluble CD54 reduced CCL3 and CCL4 production by RPE cells, and inhibition of CCL3 and CCL4 on coculture with RPE cells was reduced by anti-CD54. Blocking prostaglandin E2 (PGE2) abrogated the inhibition of CCL4, but not CCL3, by RPE cells. Blocking TGFb and nitric oxide production had no effect.CONCLUSIONS. RPE cells are able to down-regulate high levels of CCL3 and CCL4 production by T lymphocytes by using the soluble mediators sCD54 and PGE2. Reducing this production of CCL3 and CCL4 will dampen down the cascade effect and recruitment of more inflammatory cells, protecting the retina from an excessive immune response. (Invest Ophthalmol Vis Sci. 2013;54:722-730)

show abstract

Effect of anti‐macrophage inflammatory protein‐1α on leukocyte trafficking and disease progression in experimental autoimmune uveoretinitis

Cited by 27 publications

References 30 publications

Critical but divergent roles for CD62L and CD44 in directing blood monocyte trafficking in vivo during inflammation

Critical but divergent roles for CD62L and CD44 in directing blood monocyte trafficking in vivo during inflammation

The role of chemokines and their receptors in uveitis

Regulation of T-Lymphocyte CCL3 and CCL4 Production by Retinal Pigment Epithelial Cells

Contact Info

Product

Resources

About