Active participation of endothelial cells in inflammation

Abstract

Leukocyte migration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules and then migrate across the vascular endothelium. Endothelial cell adhesion molecules and their counter-receptors on leukocytes generate intracellular signals. This review focuses on the active function of endothelial cells during leukocyte-endothelial cell interactions. We include a discussion of the "outside-in" signals in endothelial cells, which are stimulated by antibody cross-linking or leukocyte binding to platelet-endothelial cell adhesion molecule-1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. Some of these signals in endothelial cells have been demonstrated to actively participate in leukocyte migration. We suggest that some of the adhesion molecule signals, which have not been assigned a function, are consistent with signals that stimulate retraction of lateral junctions, stimulate endothelial cell basal surface adhesion, or induce gene expression.

Surface Engineering of Quantum Dots for In Vivo Vascular Imaging

“…QD-IgG that were nonspecific in reactivity did not bind to retinal vasculature (Figure 6), which suggests that Fc-blocked QD-antibody bioconjugates feature reduced nonspecific binding tendencies while retaining the native binding affinity conferred by the mAb. Our technique, employing PEGylation, 2-MEA reduction, and Fcblockade by Fc-specific F(ab) 2 , is a rapid, cost-effective method for the site-specific bioconjugation and immune-shielding of mAb on nanoparticle surfaces. The 2-MEA reduction process was found to work equally well on mouse IgG 1 and IgG 2a subclasses using the same protocol.…”

“…As an alternative to removal of the Fc fragment from the antibody, we choose instead to adsorb it with an antibody fragment which itself has no Fc region. Nontargeted QD-IgG conjugates adsorbed with an Fc-blocking F(ab) 2 were less susceptible to nonspecific binding to leukocyte and endothelial cell surfaces compared to the same conjugates without Fcblockade (Figure 1-Figure 3). This may be the result of steric inhibition conferred upon the bioconjugate by the F(ab) 2 , which reduces Fc receptor access to its Fc fragment binding site on the IgG.…”

“…Herpes Simplex Virus type 1 (HSV-1), when bound by an IgG, uses its Fcγ receptors to occupy the Fc fragment of the same IgG, thus preventing Fc-mediated immunodefensive mechanisms (37). By adsorption of the QD-IgG conjugate with an Fctargeted F(ab) 2 , it is likely that the adsorbed fragment makes the Fc binding site of the targeting antibody sufficiently inaccessible to immune surveillance, thus enhancing specificity and circulation time.…”

Direct Leukocyte Migration across Pulmonary Arterioles and Venules into the Perivascular Interstitium of Murine Lungs during Bleomycin Injury and Repair

“…20,51,52 However, because leukocyte migration is largely dependent on expression of adhesion molecules on endothelium such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), 53,54 immunostaining for ICAM-1 and VCAM-1 was performed. Briefly, cryosections were fixed with methanol with 1% H 2 O 2 (SigmaAldrich) for 10 minutes at 4°C to block endogenous peroxidase activity, then were rinsed with phosphatebuffered saline (PBS), permeabilized with 0.8% Triton X-100 (Sigma-Aldrich) for 10 minutes at room temperature, and rinsed again with PBS.…”

“…Thus, PMN transmigration within larger pulmonary vessels appears consistent with patterns described for smaller postcapillary venules. 53,54 …”