| First Author | Norman MU | Year | 2005 |
| Journal | Br J Pharmacol | Volume | 144 |
| Issue | 2 | Pages | 265-74 |
| PubMed ID | 15655512 | Mgi Jnum | J:110075 |
| Mgi Id | MGI:3639067 | Doi | 10.1038/sj.bjp.0706081 |
| Citation | Norman MU, et al. (2005) TNF regulates leukocyte-endothelial cell interactions and microvascular dysfunction during immune complex-mediated inflammation. Br J Pharmacol 144(2):265-74 |
| abstractText | 1. The aim of this study was to assess directly the role of TNF in immune complex-induced leukocyte-endothelial cell interactions and microvascular dysfunction. 2. Intravital microscopy was used to examine immune complex-induced leukocyte rolling, adhesion and emigration and microvascular permeability in cremasteric postcapillary venules in wild-type and TNF(-/-) mice. The reverse passive Arthus (RPA) reaction was used to localize immune complex formation to the cremaster muscle. 3. In wild-type mice, immune complex deposition induced a reduction in leukocyte rolling velocity and increases in leukocyte adhesion and emigration. In TNF(-/-) mice, the immune complex-induced reduction in leukocyte rolling velocity was significantly attenuated, and leukocyte adhesion and emigration were also significantly reduced relative to responses in wild-type mice. 4. The alterations in TNF(-/-) mice were associated with decreased expression of endothelial P-selectin and VCAM-1, and an absence of E-selectin-dependent rolling normally seen in wild-type mice at the peak of the response. In addition, the level of immune complex-induced microvascular permeability was attenuated in TNF(-/-) mice. 5. These findings demonstrate that in immune complex-induced inflammation, TNF promotes leukocyte rolling and adhesive interactions, and entry of leukocytes into sites of immune complex deposition, in part via the increased expression and/or function of endothelial P-selectin, E-selectin and VCAM-1. In addition, this increase in leukocyte recruitment mediated by TNF correlates directly with an increase in microvascular injury. |
