Leukocytes tethering

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. 

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-... 

The inflammatory response is initiated by stimuli released from sites of tissue injury that results in the expression of selectins on the endothelial layer. These selectins (E(endothelial)-selectin and P(platelet)-selectin) function through recognition of oligosaccharides on the opposing leukocyte cell surface [194]. This interaction eventually weakly tethers the leukocyte to the endothelial layer, at which point integrin binding events lead to firm adhesion and extravasation of the leukocyte into the tissue. In certain disease processes, excessive leukoc)4e infiltration becomes deleterious to the body, and inhibitors of this process are desirable. Rheumatoid arthritis, asthma, organ transplant rejection, and reperfusion injury are just a few of the cases in which these events occur [27]. 

Tethering of the monocytes by P-selection is required for their activation by RANTES. This suggests that activated platelets regulate CK secretion by monocytes in inflammatory lesions. Platelets express mRNAs for the following CKs CTAP-m, ENA-78, RANTES, and MCP-3. Platelets also express mRNAs for IL-8RA and a novel CK receptor CCR4. These results suggest that CKs may not only play an important role in platelet activation, but also influence the nature of the leukocyte infiltrate to sites of inflammation and infection/ ... 

Neurotactin, which was independent identified in 1998, is a murine homolog of fractalkine, and is highly expressed in both the central nervous system and in peripheral neurons, whereas astrocytes and microglial cells express CX3CR1 (Harrison et al., 1998). Tethering by the mucin domain appears indirectly to facilitate activation of the chemokine domain (Imai et al, 1997). Fractalkine also directly induces adhesion of leukocytes to endothelial cells in a PTX-resistant and -specific manner. Consequently, the adhesion mediated by cell-associated fractalkine appears to occur independent of activation of the chemokine domain. 

Bunting, M., Harris, E.S., McIntyre, T.M., Prescott, S.M. and Zimmerman, G.A. (2002). Leukocyte adhesion deficiency syndromes adhesion and tethering defects involving P2 integrins and selectin ligands. Curr. Opin. Hematol. 9, 30-35. 

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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