Editorial
Authors: H J Bardenheuer, M A Weigand
Journal: Cardiovascular Research (1999)

In 1824 Dutrochet first described that leukocytes can sites of inflammation and subsequent transmigration into adhere to the vascular wall and can emigrate into the tissues are an essential part of the inflammatory response. surrounding tissue. This observation was first evidence for Thereby specific and tight interactions between circulating the physical barrier function of the endothelium preventing neutrophils and endothelial cells of the entire vascular simple passive transfer of blood cells. Within the past system play a key role in the pathogenesis of systemic decade it was the particular merit of Jaffe et al. [1] to inflammatory tissue reactions possibly leading to more develop and establish the specific methods for isolation specific processes such as acute respiratory distress and cultivation of endothelial cells. Thereafter, an enormsyndrome (ARDS), immune vasculitis, atherosclerosis and ous scientific interest was directed to characterize the role tissue rejection after organ transplantation. of the vascular endothelium concerning its metabolic The specific interaction between the endothelium and activities and its functional significance under physiologic circulating leukocytes is an essential physiologic defense and pathophysiologic conditions. mechanism against infection. However, under conditions With its unique location between the interstitium on one of reperfusion of a previous ischemic organ the overshootside and the vascular space on the other side the endoing leukocyte activation and sequestration can lead to a thelium functions as a regulator of the extracellular contremendous exacerbation of tissue injury [2]. After reperfucentration of substrates such as glucose, amino acids and sion, reactive oxygen species originating from both cell lipoproteins by the action of specific carrier molecules. types have been postulated to cause immediate cellular Because of its highly active metabolism, the endothelium damage. Thereafter, this initial phase is followed by a is also a source for a variety of very potent mediators with progression phase of reperfusion injury due to subacute opposite actions. For instance, adenosine, prostacyclin, and leukocyte recruitment. Locally produced pro-inflammatory nitric oxide are potent vasodilators which are actively cytokines such as tumor necrosis factor-a (TNF-a) or produced and released by endothelial cells after certain interleukin-1b (IL-1b) can also directly contribute to tissue stimulation. On the other hand, vasoconstrictors including damage or promote leukocyte sequestration. Furthermore angiotensin II, endothelin and the endothelium-derived cytokines can directly exert negative inotropic effects on constricting factor are also released by the endothelium. the heart which are mediated by nitric oxide [3]. Since this cell type exerts dilatory and constrictory mechaIn experimental studies leukocyte–endothelial interacnisms the endothelium occupies a key function as a tions after ischemia / reperfusion have been well charactersensitive modulator of the metabolically controlled vascuized in vascular beds of different organs including the lar tone, either locally or systemically. heart, liver and brain. Obviously, these cell–cell interacNew insights in the development of pathologic processes tions were of specific nature, because direct inhibition of have demonstrated that the vascular endothelium is activeneutrophil adhesion to the endothelium resulted in less ly involved in the maintenance of organ homeostasis by organ damage [4,5]. These data, however, await confirmae.g. its antithrombogenic features, the regulation of transtion in patients during procedures such as cardiopulmonary capillary permeability and the modulation of specific bypass (CPB), percutaneous transluminal coronary angiopimmunologic functions. The recruitment of neutrophils to lasty, carotid endarterectomy or liver transplantation. In this issue of Cardiovascular Research Zahler et al. [6] elegantly demonstrate in patients undergoing cardiopul*Corresponding author. Tel: 149-6221-56-6351; Fax: 149-6221-56monary bypass surgery that CPB not only leads to sys5531 See pages 722–730. temic inflammation, but also to an inflammatory response