Inflammation selectins

Frequently, the EAR is followed by a late phase response 4-6 h later and it is caused by the pulmonary sequestration of eosinophils, neutrophils, mast cells, and T-lymphocytes. This leukocyte recruitment depends on mast cell-derived mediators such as TNFa and various chemokines, as well as on the expression of adhesion molecules on leukocytes (e.g. VLA-4, CD11/18) and vascular endothelial cells (e.g. VCAM-1, ICAM-1, E-selectin). Products of these leukocytes have several functions First, they cause the second phase of bron-choconstriction, mucus secretion, and airway swelling second, they cause tissue destruction third, they launch and entertain the chronic inflammation. 

Inflammation. Figure 1 Sequence of events in the recruitment of leukocytes in postcapillary venules adjacent to injured tissue. At the site of lesion, diverse reactive substances stimulate the endothelium to produce inflammatory cytokines, chemoattractants and other inflammatory mediators. The cytokine-activated endothelium expresses adhesion molecules that lead to the low affinity interactions between leukocytes and endothelium, which is mediated by selectins and described as rolling. Subsequently integrins mediate the firm adhesion of leukocytes, which allows emigration of the cells from venules into the interstitial compartment. Activated mast cells, PMNs and macrophages secrete cytokines (TNFa), lipid mediators (LTB4) and other inflammatory players (histamine, NO). 

Selectins Play Key Roles in Inflammation in Lymphocyte Homing... 

Nemmar, A. et al. (2007) Enhanced peripheral fhrombogenidty after lung inflammation is mediated by platelet-leukocyte activation role of P-selectin. Journal of Thrombosis and Haemostasis,... 

Ohno N, Ichikawa H, Coe L, Kvietys PR, Granger DN, Alexander JS. Soluble selectins and ICAM-1 modulate neutrophil-endothelial adhesion and diaped-esis in vitro. Inflammation. 1997 21 313-324. 

The interest in using saccharide-substituted polymers to bind and cluster cell surface proteins arises from studies of L-selectin, a protein involved in inflammation. L-selectin binds glycoproteins that display complex carbohydrates, and... 

Our group is focused upon applications dealing with inhibitions of bacterial (E. coli, Streptococcus suis) and viral (flu) infections, selectins involved in inflammation processes, acute rejection following xenotransplantation, homing of... 

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]. 

The recruitment and migration of leucocytes into inflamed tissues is a carefully orchestrated process (Figure 7.1). It consists of sequential steps mediated by different families of adhesion molecules expressed by both the leucocytes and the endothelial cells at the site of inflammation [4]. Of these adhesion molecules, the selectin family mediates the initial contact and subsequent rolling of the leucocyte on the endothelium. It consists of three members, i.e. E- (endothelial), P- (platelet) and L- (leucocyte) selectin. Activated endothelial cells express E- and P-selectin. P-selectm is also expressed on platelets, whereas L-selectin is only expressed on subsets of leucocytes [5]. 

Recently, monoclonal antibodies were attached to gas-filled microbubbles using this spacer coupHng technology. Testing in vitro, in a cell culture system, demonstrated selective accumulation of decafluorobutane-based lipid shell MP1950 microbubbles with covalently attached anti-lCAM-1 antibodies, onto the surface of activated endotheUum [8]. Anti-P-selectin antibodies attached to such microbubbles via an avidin-biotin scheme showed selective accumulation in the areas of inflammation and ischemia/reperfusion injury in an animal model [93]. In the latter example, biotin was also connected to the microbubble surface via a flexible polymer spacer arm. 

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). 

Selectins are a family of plasma membrane lectins that mediate cell-cell recognition and adhesion in a wide range of cellular processes. One such process is the movement of immune cells (T lymphocytes) through the capillary wall, from blood to tissues, at sites of infection or inflammation (Fig. 7-33). At an infection site, P-selectin on the surface of capillary endothelial cells interacts with a specific oligosaccharide of the glycoproteins of circu-... 

L. A. Lasky, Selectins Interpreters of cell-specific carbohydrate information during inflammation, Science 258 964 (1992), and references therein,... 

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