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Review
. 1999 Feb;126(3):537-50.
doi: 10.1038/sj.bjp.0702328.

Leukocyte-endothelial cell adhesion: avenues for therapeutic intervention

J Panés  1 , M Perry, D N Granger
Affiliations
Review

Leukocyte-endothelial cell adhesion: avenues for therapeutic intervention

J Panés et al. Br J Pharmacol. 1999 Feb.
No abstract available

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Figures

Figure 1
Figure 1
Steps in the recruitment of leukocytes in postcapillary venules. (A) illustrates that in the absence of an inflammatory stimulus, leukocytes are largely flowing in the stream of red cells with no adhesive interactions with venular endothelium. (B) illustrates the low affinity interaction between leukocytes and endothelium that is mediated by selectins and manifested as rolling. (C) illustrates that activation of leukocytes and/or endothelial cells can result in stationary adhesion of leukocytes. (D) illustrates that firmly adherent leukocytes can emigrate from venules into the adjacent interstitial compartment, usually along a chemotactic gradient.
Figure 2
Figure 2
Mechanisms underlying the expression of adhesion molecules on leukocytes and endothelial cells at the onset of inflammation. Perivascular cells such as mast cells and macrophages initiate the response by releasing a variety of inflammatory mediators. Engagement of lipid mediators (LTB4 and PAF) with receptors on neutrophils results in the activation of β2-integrins (CD11/CD18). Engagement of histamine with its receptor (H1) on endothelial cells results in the rapid mobilization of preformed P-selectin from its storage site (Weibel-Palade bodies). Engagement of cytokines (e.g., TNFα) to their receptors on endothelial cells lead to the activation of nuclear transcription factors (e.g., NF-κB) that stimulates the synthesis of adhesion glycoproteins, such as VCAM-1, ICAM-1, and E-selectin, which are subsequently expressed on the cell surface.
Figure 3
Figure 3
Mechanisms used by the glucocorticoid receptor to inhibit transactivation by transcription factors. (1) After the glucocorticoid (GC) activates its receptor (GR), a direct protein-protein interaction between GR and transcription factors (TF) will prevent the binding of TF to the respective DNA response elements. (2) Binding of GR to the promoter region of the IκB gene results in transactivation; IκB binding NF-κB will prevent binding or displace NF-κB from κB sites. (3) Binding of GR to glucocorticoid responsive elements modulates TF-induced transactivation.
Figure 4
Figure 4
Target sites for decoy and antisense ODNs. Antisense ODNs are single stranded DNA sequences that specifically bind to mRNA, thereby blocking expression of the gene product. Transcription factor (TF) decoys are double stranded ODNs that compete for protein binding with the authentic binding elements, thereby interfering with gene regulation.
See this image and copyright information in PMC

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