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TNF regulates leukocyte–endothelial cell interactions and microvascular dysfunction during immune complex‐mediated inflammation
Author(s) -
Norman M Ursula,
Lister Karyn J,
Yang Yuan H,
Issekutz Andrew,
Hickey Michael J
Publication year - 2005
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706081
Subject(s) - intravital microscopy , immune system , cremaster muscle , inflammation , tumor necrosis factor alpha , immunology , immune complex , microcirculation , cell adhesion , endothelial activation , endothelial dysfunction , microbiology and biotechnology , vascular permeability , endothelial stem cell , chemistry , biology , adhesion , medicine , endocrinology , in vitro , biochemistry , organic chemistry
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.British Journal of Pharmacology (2005) 144 , 265–274. doi: 10.1038/sj.bjp.0706081