The vessel wall and its interactions

Abstract

Historical overviewThe interactions of leukocytes and platelets with the vessel wall, such as occur in inflammation, are highly dynamic and often transient. The development of intravital microscopy was the spark that allowed real-time observations of blood cells in live animals, and led to the detection and molecular analyses of their interactions with the vessel wall. Rudolph Wagner first published in 1839 a description of leukocytes interacting with the vessel wall. 1 In blood vessels of the webbed feet of a grass frog, he observed that leukocytes (then called lymph-corpuscles) in venules were moving in close contact with the vessel wall, and more slowly than other blood cells. The drawing in Figure 1 likely represents the first depiction of rolling leukocytes; we now know that leukocytes roll constitutively in venules of the skin.A few years later the frog-this time its spread tongue-was again central to another milestone microscopic observation. Augustus Waller noted that the trauma caused by the pins and the long exposure to ambient air produced a tongue irritation that triggered the adhesion of lymph-corpuscles onto the vessels of the microcirculation. He also noted that as time passed more of them "escaped" into the surrounding tissue while scarcely any red blood cells (RBCs) could be seen outside the vessel. Waller remarked on "the restorative power of blood which immediately closes the aperture" formed by the extravasating leukocytes and proposed that pus has its origin from these colorless extravasated corpuscles. 2 It took 40 years for defined theories to attempt to explain what initiates these inflammatory responses. In his Lectures on General Pathology, Julius Cohnheim stated "we have here to deal with a molecular change of the vessel walls. . . comprised under the notion and name of inflammation." 3 Cohnheim attributed everything to alterations in the endothelium and noted that inflammatory changes did not affect blood as the vessel wall could be modified even if blood were replaced by saline before ligation. In contrast, at about the same time, Elie Metchnikoff concentrated on "the fundamental importance of phagocytosis in inflammation." In this phagocytic theory of inflammation, he suggested that phagocytes were crucial to destroy the "irritant bodies." 4 Although Metchnikoff stated that "inflammation may occur without any intervention of the blood vessels," he hinted at the need for leukocyte activation as "these cells are in the first place affected by various substances which posses an attraction for them." Clearly, these brilliant scientists were equally right as it is now known that both endothelial and leukocyte activation are key to the inflammatory response.Following vascular injury, the rapid coalescence of blood platelets into forming thrombi was observed by intravital microscopy in the late 1800s (reviewed in Jackson 5 ). The adhesion of platelets to presumably intact but stimulated endothelium was documented only in 1970 by Begent and Born. 6 After ADP application to the outside of a ...

In vitro microvessels for the study of angiogenesis and thrombosis

“…In healthy scenarios, the endothelium provides a nonadhesive and antithrombotic interface for the transport of blood through the vessel whereas during inflammation, the endothelium promotes the formation of the thrombi via local expression and secretion of adhesive proteins (33). The interaction of blood with endothelium has been studied extensively in vitro in planar formats that lack appropriate vessel geometries or a 3D matrix (34,35).…”

Free Fatty Acid Causes Leukocyte Activation and Resultant Endothelial Dysfunction Through Enhanced Angiotensin II Production in Mononuclear and Polymorphonuclear Cells

“…It is reasonably assumed that the release of cytokines and reactive oxygen species from activated T lymphocytes, which has been shown to be Ang dependent, 30 may also adversely modulate vascular function. 31 The extrapolation of our results to patients with visceral fat obesity is not necessarily straightforward. Individuals with visceral fat obesity have chronically elevated FFA levels.…”

Engagement of αIIbβ3 (GPIIb/IIIa) with ανβ3 Integrin Mediates Interaction of Melanoma Cells with Platelets

“…In contrast, we observed a robust increase in adhesivity of murine and human melanoma cells in the presence of platelets in various settings in vitro. Adherent platelets present potent adhesion receptors such as JAM-C, P-Selectin, GPIb␣, or GPIIb/IIIa to other circulating cells providing a platform for a potent cellular bridging mechanism to the vascular wall (20,25,(52)(53)(54)(55)(56). Recently, glycoprotein Ib␣ (GPIb␣), the second most abundant receptor expressed on platelets, has been reported to be significantly involved in melanoma metastasis, as the functional absence of GPIb␣ correlated with a clear reduction in the number of lung metastatic foci in vivo (57).…”