Carbohydrate-binding proteins leukocytes

Thirdly, there are the selectins, a family of Ca Mependent carbohydrate-binding proteins which function to control leukocyte interactions with vascular endothelium (Tedder et al, 1995). There are three closely related members of the selectin family, namely L (leukocyte)-, P (platelet)-, and E (endothelial)-selectin. P-selectin is expressed in the Weibel-Palade bodies of endothelial cells and in the a-granules of platelets. It is rapidly mobilized to the sur ce of endothelial cells and platelets in response to a variety of inflammatory agents such as fiuombin, histamine, complement factors, fiee radicals and cytokines (Tedder et al, 1995). P-selectin mediates the adhesion of neutrophils and monocytes to activated platelets and endothelial cells. Platelets can be bound to the endothelium indirectly by adhering to leukocytes bound to the endothelium. 

These interactions involve adhesion proteins called selectins, which are found both on the rolling leukocytes and on the endothelial cells of the vascular walls. Selectins have a characteristic domain structure, consisting of an N-terminal extracellular lectin domain, a single epidermal growth factor (EGR) domain, a series of two to nine short consensus repeat (SCR) domains, a single transmembrane segment, and a short cytoplasmic domain. Lectin domains, first characterized in plants, bind carbohydrates... 

E-selectin recognises and binds to sialylated carbohydrates present on the surface proteins of certain leukocytes. The local release of cytokines IL-1 and TNF induces the overexpression of E-selectin on the endothelial cells of nearby blood vessels. Leukocytes with a low affinity for E-selectin will slow and roll along the internal surface of the vessel. 

White blood oells oontinually patrol the circulatory system and interstitial spaces, ready for mobilization at a site of trauma. The frontline scouts for leukocytes are carbohydrate groups on their surface called sialyl Lewis acids. When injury occurs, cells at the site of trauma display proteins, called selectins, that signal the site of injury and bind sialyl Lewis acids. Binding between selectins and the sialyl Lewis acids on the leukocytes causes adhesion of leukocytes at the affected area. Recruitment of leukocytes in this way is an important step in the inflammatory cascade. It is a necessary part of the healing process as well as part of our natural defense against infection. A molecular model of a sialyl Lewis acid is shown below, and its structural formula is given in Section 22.16. 

Beside qualitative detection of oligosaccharides and quantitative affinity or kinetic analyses, the in situ modification of carbohydrates immobilized at a sensor chip surface has been published [6, 19], Van der Merwe et al. [20] used this approach to analyze the binding of B-lymphocyte antigen, CD22, to the highly glycosylated leukocyte surface protein CD45. 

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