Elsevier

The Annals of Thoracic Surgery

Volume 66, Issue 6, December 1998, Pages 2135-2144
The Annals of Thoracic Surgery

Current Reviews
Effects of cardiopulmonary bypass on leukocyte and endothelial adhesion molecules

https://doi.org/10.1016/S0003-4975(98)00727-9Get rights and content

Abstract

During the inflammatory response, triggered by cardiopulmonary bypass, interaction between activated leukocytes, platelets, and endothelial cells is mediated through the expression of three main groups of adhesion molecules: the selectins, the integrins, and the immunoglobulin superfamily. The selectins, which mediate the initial rolling of the leukocyte on the endothelium, are divided in three subgroups: L-selectin is expressed on all three leukocyte types, P-selectin is expressed on platelets and endothelial cells, and E-selectin is only expressed on endothelial cells. Integrins can be found on most cell types, consist of an α and a β subunit and mediate firm adhesion of the leukocyte and migration into the tissues. They are classified into subgroups according to the type of their β subunit. Immunoglobulins such as ICAM-1 and VCAM-1 are expressed mainly on endothelium and act as ligands for certain integrins. This review article summarizes the existing, and rapidly expanding, literature concerning the effects of cardiopulmonary bypass on the expression of leukocyte and endothelial adhesion molecules. Deeper understanding of the behavior and the role of adhesion molecules during cardiopulmonary bypass may facilitate effective intervention in the inflammatory response process and suppression of its adverse effects.

Section snippets

Systemic inflammatory response and cardiopulmonary bypass

The highly regulated cellular and humoral defense mechanism of the organism against potentially threatening situations is often proved to be hazardous for the host, causing “exaggerated” inflammatory response. Surgeons are often faced with conditions associated with localized or systemic inflammation. These conditions include inflammatory processes such as sepsis and pancreatitis, response to major trauma and major surgery, ischemia–reperfusion, burn, shock, or more specific reactions such as

Adhesion molecules

More than 100 years ago scientists documented the fact that leukocytes bind to endothelium before they transmigrate into sites of inflammation. However, a deeper understanding of the molecular mechanisms involved in leukocyte adhesion has developed only in the past decade. Specific adhesion molecules, which are expressed on leukocytes, platelets, and endothelial cells, were shown to participate in this process [26]. Leukocyte activation with expression of adhesion molecules also takes place

Selectins

The initial contact in the leukocyte adhesion cascade is made through the so-called rolling of the leukocyte and its loose attachment on the endothelium under hydrodynamic shear flow, by glycoproteins named selectins, the primary sequence of which was first described in 1989 [28]. The selectins comprise a group of three molecules that are closely related in structure and function (Table 1): L-, E-, and P-selectin.

Integrins

Integrins comprise the largest group of adhesion receptors and are found on most cell types, including leukocytes. They are transmembrane cell-surface proteins that respond to signals of cellular activation, and mediate their function by binding to specific ligands. Each integrin contains a noncovalently associated α and β chain, with characteristic structure [61]. Integrins are classified into subgroups based on the β chain. Table 5 shows the members of the integrin family that are expressed

Immunoglobulin superfamily

Adhesion molecules of the immunoglobulin superfamily are transmembrane glycoproteins that are expressed mainly by endothelial cells, which participate in cell adhesion by serving as ligands for certain leukocyte integrins. Intracellular adhesion molecule-1 (ICAM-1) is one of the primary ligands for the β2-integrins, whereas VCAM-1 binds to α4β1. ICAM-1 and VCAM-1 increase their expression after endothelial cell P-selectin has been shed and can remain upregulated for days [78].

Preoperative

Conclusions

Adhesion molecules have established their role as important inflammatory mediators in studies of the inflammatory response to CPB. They have been increasingly the focus of investigation and have been shown to undergo changes of different extents during and after CPB. However, there are still several gaps in our knowledge. Although the upregulation patterns of the neutrophil β2 integrins are becoming clear, the role of the β1 integrins is still not defined. Furthermore, changes on lymphocytes

Acknowledgements

We thank R. Clive Landis, PhD, for his comments on the manuscript. George Asimakopoulos is supported by the British Heart Foundation.

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