Leukocyte – endothelial interactions in inflammation

Abstract

At sites of inflammation, infection or vascular injury local proinflammatory or pathogen-derived stimuli render the luminal vascular endothelial surface attractive for leukocytes. This innate immunity response consists of a well-defined and regulated multi-step cascade involving consecutive steps of adhesive interactions between the leukocytes and the endothelium. During the initial contact with the activated endothelium leukocytes roll along the endothelium via a loose bond which is mediated by selectins. Subsequently, leukocytes are activated by chemokines presented on the luminal endothelial surface, which results in the activation of leukocyte integrins and the firm leukocyte arrest on the endothelium. After their firm adhesion, leukocytes make use of two transmigration processes to pass the endothelial barrier, the transcellular route through the endothelial cell body or the paracellular route through the endothelial junctions. In addition, further circulating cells, such as platelets arrive early at sites of inflammation contributing to both coagulation and to the immune response in parts by facilitating leukocyte–endothelial interactions. Platelets have thereby been implicated in several inflammatory pathologies. This review summarizes the major mechanisms and molecules involved in leukocyte–endothelial and leukocyte-platelet interactions in inflammation.

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).…”

The Relationship between Vascular Function and the Autonomic Nervous System

“…10) The expression of adhesion molecules leads to the recruitment of leukocytes in the process of infl ammation. 11) There are various methods for measuring endothelial function, but the evaluation of ECs is complicated because one modality evaluating endothelial function can only assess a specifi c and limited aspect among the multi-potencies of the endothelium. 12) Endothelium-dependent vasomotion has been the most widely used clinical endpoint for the assessment of endothelial function.…”

Protein Kinase C-θ Is Required for Murine Neutrophil Recruitment and Adhesion Strengthening under Flow

“…To get to the site of inflammation, neutrophils follow a sequence of well-orchestrated events. This adhesion cascade involves tethering, rolling and slow rolling, arrest, adhesion strengthening and intravascular crawling, and transmigration through the endothelium, followed by migration through the tissue (1,2).…”