Inflammatory cell adhesion molecules induction

Induction of Inflammatory Cell Adhesion Molecules AND Monocyte-Endothelial Interactions... 

SECs, like the vascular endothehum, play an active part in the control of leucocyte recruitment in cases of acute and chronic inflammatory conditions. Eeucocyte recruitment from the blood compartment is a crucial determinant for the induction of immunity and inflammation. SECs control this process by producing cytokines that activate leucocytes and by expressing adhesion molecules. Under inflammatory conditions upregulation of intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) was found [35 36], as well as expression of E-selectin and P-selectin [37]. Together with the expression of CD4 on SECs it has been postulated that these adhesion molecules might also be involved in the adhesion of KC cells to the sinusoidal wall [20]. 

Therapeutic irradiation is known to have multiple interactions with the vasculature of the irradiated tissue (12). Radiation has direct cytotoxic effects on the vascular endothelium, likely due to induction of oxidative injury. Radiation-induced injury stimulates inflammation and influx of inflammatory cells in addition to creating aprocoagulant state in the vascular space by the transcriptional induction of tissue factor with the subsequent activation of coagulation factors as well as von Willebrand factor and platelets. Experimental evidence suggests that the mechanism by which radiation initiates these responses is in part through the induction of cell-adhesion molecules including ICAM-1, E-selectin, and P-selectin and in part through local cytokine production and release (13). 

Halichlorine (1) (Fig. 11.1) is an alkaloid which was isolated from the marine sponge H. okadai Kadota (Kuramoto et ah, 1996). This compound was revealed to be a novel alkaloid containing an azaspiro[4.5]decane skeleton clarified by detailed spectroscopic analyses. The absolute stereostructure was confirmed by many synthetic studies (Arimoto et ah, 1998 Clive et ah, 2005 Liu et ah, 2009 Trauner et ah, 1999). Halichlorine was shown to inhibit the induction of vascular cell adhesion molecule-1 (VCAM-1) in cultured human umbilical vein endothelial cells. Drugs that block the inflammatory stimuli-induced expression of VCAM-1 may be useful for treating atherosclerosis, coronary artery diseases, angina, and noncardiovascular inflammatory diseases (Kock et ah, 1995). We introduce here the recent aspects of the biological and physiological activities of halichlorine. 

The quinolizidine alkaloid halichlorine (203), isolated from the marine sponge Halichondria okadai, inhibits the induction of vascular cell adhesion molecule-1 (VCAM-1) at IC50 7 pg/ml, which may be useful for treating atherosclerosis, coronary artery diseases, angina and noncardiovascular inflammatory diseases [161]. 

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. 

PAMPs and various tissue factors can prime DCs to produce T-cell-polarizing factors [21], IL-12 is a pro-inflammatory cytokine that induces IFN-y and promotes the development of Thl-cell differentiation [31], Other Thl-polarizing factors are IFN-a and IFN-(3 [32] and cell-surface expressed intracellular adhesion molecule (ICAM)-l [33]. On the other hand, it has been shown that NF-kB inducing kinase (NIK), which is known to regulate B-cell maturation and lymphoid organogenesis, is important for the induction of Thl7 cells [34],... 

TNF-a and IL-1 are current targets of antiinflammatory drug therapy. A homotrimer of 17-kDa protein subunits whose effects include the activation of neutrophils and eosinophils, induction of COX-2, induction of proinflammatory cytokines (e.g., IL-1, IL-6), enhancement of endothelial layer permeabihty, induction of adhesion molecules by endothelial cells and leukocytes, stimulation of fibroblast proliferation, degradation of cartilage, and stimulation of bone reabsorption. Two receptors mediate these effects a 55-kDa receptor (p55) and a 75-kDa receptor (p75). Each of these receptors is found in both cell surface and soluble forms. The binding of two or three cell surface receptors to TNF-a initiates an inflammatory response. Soluble p55 also acts as a signaling receptor for inflammatory responses, whereas soluble p75 acts as an antagonist. 

Various adhesion molecules are reported to be expressed on vascular endothelial cells at sites of inflammation (Libby, 2002). In fact, VCAM-1, expressed on the surface of vascular endothelial cells in response to inflammatory stimuli, is suggested to play an important role in leukocyte recruitment (Gerrity et al, 1979). The adhesion of monocytes to vascular endothelial cells is the first critical step in the induction of atherosclerosis (Glass and Witztum, 2001). Supportively, the expression of VCAM-1 is reported to increase in atherosclerosis lesions (Cybulsky and Gimbrone,... 

Oxidised LDL in the artery wall initiates a series of reactions designed to repair the damage it causes. Initial damage triggers an inflammatory response. Monocytes enter the artery waU from the bloodstream, with platelets adhering to the area of insult. This may be promoted by induction of factors such as vascular ceU adhesion molecule 1 (VCAM-1), a cell-surface sialoglycoprotein that is expressed by cytokine-activated endothelium. This membrane protein mediates leukocyte-endothelial cell adhesion and signal transduction, and may play a role in the development of atherosclerosis and rheumatoid arthritis. 

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]. 

Modulation of the expression and function of vascular graies is yet another effect exerted by oxLDLs by which these genes may participate in inflammatory and atherosclerotic processes. OxLDL increases the VCAM-1 induction response to a cytokine inflammatory signal in endothehal cells from different vaseular beds. More recently, oxLDLs have been shown to stimulate intercellular adhesion molecule (ICAM-1) expression in EC and monocyte adhesion, probably through activation of a speciflc protein tyrosine kinase (PTK). ... 

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