Transendothelial migration

IFN- 3 reduces the induction by inflammatory cytokines of adhesion molecules and of MHC class I and II complex on endothelial cells, a process preceding attachment and transendothelial migration of T-cells. These anti-inflammatory effects of IFN- 3 exemplify antagonistic actions of type I and type IIIFN. There is, indeed, much clinical evidence for the involvement of IFN-y in inflammatory processes - through activation of iNOS and subsequent secretion of NO - leading to the establishment of autoimmune diseases as for instance in rheumatoid arthritis. 

MasUn CL, Kedzierska K, Webster NL, Muller WA, Crowe SM (2005) Transendothelial migration of monocytes the underlying molecular mechanisms and consequences of HlV-1 infection. Curr HIV Res 3(4) 303-317... 

Peled A, Kollet O, Ponomaryov T, et al. The chemokine SDF-1 activates the inte-grins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells role in transendothelial/stromal migration and engraftment of NOD/SCID mice. Blood 2000 95( 11) 3289-3296. 

Dzenko KA, Song L, Ge S, et al. CCR2 expression by brain microvascular endothelial cells is critical for macrophage transendothelial migration in response to CCL2. Microvasc Res 2005 90(l-2) 53-64. 

ICAM-1 and -2 are constitutively expressed on endothelial cells ICAM-1 may be further up-regulated by exposure to cytokines. ICAM-3 has recently been described (its identity based on the unique specificity of a monoclonal antibody) and is a 124-kDa glycoprotein present on the surfaces of T cells, monocytes and neutrophils its expression may be up-regulated by stimulants such as mitogens. VCAM-1, which is expressed on the luminal surface of cytokine-exposed endothelial cells, binds T cells via VLA-4. It is also expressed on the surface of some leukaemic cell lines, on rheumatoid synovial cells and on some tumours.On the other hand, ICAM-1 is found on all endothelial surfaces, and its interaction with neutrophil integrins is the major mechanism that results in the stimulation of transendothelial migration. 

Smith, W. B., Gamble, J. R., Clark-Lewis, I., Vadas, M. A. (1991). Interleukin-8 induces neutrophil transendothelial migration. Immunol. 72,65-72. 

Klunker S, Trautmann A, Akdis M, Verhagen J, Schmid-Grendelmeier P, Blaser K, et al A second step of chemotaxis after transendothelial migration keratinocytes undergoing apoptosis release IP-10, Mig and iTac for T cell chemotaxis towards epidermis in atopic dermatitis. J Immunol 2003 171 1078-1084. 

Rusama T, Mukai M, Tatsuta M et al (2006) Inhibition of transendothelial migration and invasion of human breast cancer cells by preventing geranylgeranylation of Rho. Int J Oncol 29 217-223... 

Andjelkovic AV, Zochowski MR, Morgan F et al (2001) Qualitative and quantitative analysis of monocyte transendothelial migration by confocal microscopy and three-dimensional image reconstruction. In Vitro Cell Dev Biol Anim 37 111-120... 

Engelhardt, B., and H. Wolburg. 2004. Transendothelial migration of leukocytes Through the front door or around the side of the house Eur J Immunol 34 2955. 

Srikrishna G, Panneerselvam K, Westphal V, Abraham V, Varki A, Freeze HH. 2001. Two proteins modulating transendothelial migration of leukocytes recognize novel carboxylated glycans on endothelial cells. J Immunol 166(7) 4678-4688. 

Faveeuw C, Preece G, Ager A, Transendothelial migration of lymphocytes across high endothelial venules into lymph nodes is affected by metalloproteinases, Immunobiology 2001 98(3) 688—695. 

Vachula, M. and van Epps, D. E. (1992). In vitro models of lymphocyte transendothelial migration. Invasion Metastasis 12, 66-81. 

The iron or haemoprotein catalysed oxidative reactions may mediate the responses associated with acute and chronic inflammation. In the post-ischaemic, reperfused heart the role of oxidant stress has been linked with increases in leucocyte adhesion and transendothelial cell migration from oxidant production within the microcirculation [115]. This is probably caused by an increased expression in adhesion molecules or the fixation of transiently expressed adhesion molecules by the peroxidation of membrane lipids which reduces membrane fluidity [117,118]. This oxidant stress may also lead to apoptosis induction, DNA damage, inflammatory mediator synthesis and regulate gene expression [119,120,121]. 

Nottet HS, Persidsky Y, Sasseville VG, Nukuna AN, Bock P, Zhai QH, Sharer LR, McComb RD, Swindells S, Soderland C, Gendel-man HE (1996) Mechanisms for the transendothelial migration of HIV-1-infected monocytes into brain. J Immunol 156 1284-1295. 

A transendothelial migration step following firm adhesion. 

Oppcnheimer-Marks, N., Davis, L.S., Brogue, D.T., Rambetg, J. and Lipsky, P.E. (1991). Differential utilization of ICAM-1 and VCAM-1 during the adhesion and transendothelial migration of hiunan T lymphocytes. J. Immunol. 147,2913. 

Eosinophil transendothelial migration induced by cytokines. I. Role of endothelial and eosinophil adhesion molecules in IL-lj8-induced transendothelial migration. J. Immunol. 149, 4021-4028. 

Chemokines in Leukocyte Trafficking CKs are thought to be centrally involved in leukocyte trafficking and not limited to attraction of monocytes by the CC family and neutrophils by the CXC family. Other functions of the CKs include expression of adhesion molecules, especially for the lymphocytes in both the migratory response and maturation and proliferation. The selective chemoattractant qualities shown by CKs explain the directed migration of each kind of leukocyte or even of subtypes of these cells (as T and B lymphocytes, perhaps even Thl and Th2). Several studies have shown that CC CKs attract T lymphocytes and that CD45R0, memory-phenotype cells are considered to be the main responders. The results, however, have often been contradictory, and the role of lymphocyte activation and proliferation is still unclear. The CC CKs MCP-2, MCP-3, RANTES, MIP-la, MIP-lp, and MCP-1 induce significant, dose-dependent transendothelial chemotaxis of... 

In conclusion, this section has highlighted the potential pathogenic contribution of blood neutrophils to the CNS injury that accompanies the ischaemia-reperfusion injury of stroke. From experimental models of this disorder, it appears that the second wave of tissue damage is induced either by neutrophil-mediated vasoocclusion or by the infiltration of neutrophils into the ischaemic tissue with concomitant release of lytic factors. Antagonising both neutrophil attachment to endothelium and the transendothelial migration of these cells at the level of the blood-brain barrier is likely to be of clinical benefit to cerebral ischaemia-reperfusion injury. Consequently, it is anticipated that a further unravelling of the mechanisms that promote neutrophil interaction with cerebral vessel walls will lead to the introduction of a more specific therapeutic intervention for the treatment of stroke. 

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