Leukocyte tethering and rolling

Somers, W T, Tang, J, Shaw, G D, Camphausen, R T, Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound S Le(x) and PSGL-1, Cell., 103, 467-479, 2000, and references cited therein. 

Selectins are transmembrane proteins with membrane-distal Ca +-dependent lectin domains. This family of cell adhesion molecules is involved in the tethering and rolling of leukocytes on the blood vessel endothelium. Nicholson and colleagues [10] published the analysis of leukocyte selectin, CD62L, binding to the mucin-like glycoprotein, Gly-CAM-1. 

Requirements for Selectins to Mediate Tethering and Rolling of Leukocytes under Hydrodynamic Flow... 

The importance of seleetins in humans is underscored by the discovery of a congenital disorder of fucose metabolism, termed leukocyte adhesion deficiency 2 (LAD-2) [49]. Because patients with LAD-2 lack fucosylated glycoconjugates, they do not express functional selectin ligands. Leukocytes from these patients do not tether to and roll on P- or E-selectin surfaces. Clinically, the patients have more infections, supporting the concept that the selectins have an important function in initiating recruitment of leukocytes. 

The expression of selectins is normally tightly regulated to ensure that leukocytes tether to and roll on the vascular surface only at appropriate locations [53]. However, dysregulated expression of selectins has been implicated in several forms of leukocyte-mediated tissue injury [54]. 

Rolling involves sequential attachment and detachment of the leukocyte with the endothelium. The selectin receptors bind very quickly and tether via recognition of their carbohydrate moieties with the ends of flexible pro-... 

As noted earher, there is much evidence to support the statement that rolling is an absolute prerequisite to leukocyte adhesion. This is certainly true for muscle and skin tissue. However, this is not conclusive for all tissues. The Hver, lung, and heart are examples where rolling may not be necessary for leukocyte recruitment. In the lung s alveolar capillaries and the fiver s sinusoids, rolling is not observed because the vessel lumen or interstitial gap is extremely small, which allows for adhesion to occur straight from tethering. 

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