ICAMs

Rossmann suggested that the canyons form the binding site for the rhi-novirus receptor on the surface of the host cells. The receptor for the major group of rhinoviruses is an adhesion protein known as lCAM-1. Cryoelectron microscopic studies have since shown that ICAM-1 indeed binds at the canyon site. Such electron micrographs of single virus particles have a low resolution and details are not visible. However, it is possible to model components, whose structure is known to high resolution, into the electron microscope pictures and in this way obtain rather detailed information, an approach pioneered in studies of muscle proteins as described in Chapter 14. 

FIGURE 7.2 Model of LFA-1 showing the binding domain of ICAM-1 (the endogenous ligand for this protein) and the binding site for lovastatin, an allosteric modulator for this protein. Redrawn from [7],... 

Frequently, the EAR is followed by a late phase response 4-6 h later and it is caused by the pulmonary sequestration of eosinophils, neutrophils, mast cells, and T-lymphocytes. This leukocyte recruitment depends on mast cell-derived mediators such as TNFa and various chemokines, as well as on the expression of adhesion molecules on leukocytes (e.g. VLA-4, CD11/18) and vascular endothelial cells (e.g. VCAM-1, ICAM-1, E-selectin). Products of these leukocytes have several functions First, they cause the second phase of bron-choconstriction, mucus secretion, and airway swelling second, they cause tissue destruction third, they launch and entertain the chronic inflammation. 

CD163 (Scavenger receptor) Adhesion molecules (ICAM-1, E-selectin)... 

These are murine or humanized antileukocyte functional antigen (LFA)-la antibodies that block LFA-la (CDlla)-ICAM-l (CD54) interaction. 

This murine antibody also blocks LFA-la-ICAM-1 interaction. 

Members of the immunglobulin gene superfamily (VCAM-1, ICAM-1, ICAM-2)... 

PAMPs and various tissue factors can prime DCs to produce T-cell-polarizing factors [21], IL-12 is a pro-inflammatory cytokine that induces IFN-y and promotes the development of Thl-cell differentiation [31], Other Thl-polarizing factors are IFN-a and IFN-(3 [32] and cell-surface expressed intracellular adhesion molecule (ICAM)-l [33]. On the other hand, it has been shown that NF-kB inducing kinase (NIK), which is known to regulate B-cell maturation and lymphoid organogenesis, is important for the induction of Thl7 cells [34],... 

ICAM-1 and ICAM-2 regulates Th2 cytokine pro- 46 duction. J Immunol 1998 161 5138-5142. 

Key PMN, polymorphonuclear leukocytes EC, endothelial cell lymphs, lymphocytes CD, cluster of differentiation iCAM, intercellular adhesion molecule LFA-1, lymphocyte function-associated antigen-1 PECAM-1, platelet endothelial cell adhesion cell molecule-1. 

Glycoprotein llb/llla Platelets allbps ICAM-2 Fibrinogen, fibronectin, von Willebrand factor Platelet adhesion and aggregation... 

Enlimomab Acute Stroke Trial Investigators. Use of anti-icam-1 therapy in ischemic stroke results of the enlimomab acute stroke trial. Neurology 2001 57 1428-1434. 

Wang GJ, Deng HY, Maier CM, Sun GH, Yenari MA. Mild hypothermia reduces ICAM-1 expression, neutrophil infiltration and microglia/monocyte accumulation following experimental stroke. Neuroscience 2002 114 1081-1090. 

Sustained NF-kB activation, TNF-a, IL-1, proliferation, signals (M-CSF, G-CSF), chemotaxis (MCP-1), adhesion (VCAM-1, ICAM-1), thrombogenesis (TF)... 

The cell-to-cell interaction following the expression of adhesion molecules (ICAM-1, VCAM-1 and selectin) in endothelial cells induced by cytokines treatment has been reported to be blocked by hydroflavones and flavanols. Apigenin, the most potent flavone tested in this study, inhibited the expression... 

Gentile, C. et al.. Antioxidant betalains from cactus pear (Opuntia ficus- indica) fruit inhibit endothelial ICAM-1 expression, Ann. NY Acad. ScL, 1028, 481, 2004. 

Oxidatively modified LDL up-regulates the surfece expression of VCAM-1 and intracellular adhesion molecule-1 (ICAM-1) in cultured endothelial cells, promoting the interactions between both cell types (Kume et al., 1992). This may play a pivotal role in the development of atherosclerosis by promoting the penetration of circulating monocytes into the suben-dothelial space whilst inhibiting the mobility of resident macrophages. It has been previously demonstrated that ICAM-1, E-selectin, and VCAM-1 are up-regulated in the microvasculature of rheumatoid but not control synovium (Corkill et al., 1991 Koch et al., 1991). The association between ox-LDL and increased expression of adhesion molecules in the inflamed synovium has yet to be studied. 

An anti-intracellular adhesion molecule-1 (anti-ICAM-1) antibody reduced neurological damage in a rabbit embolic model of stroke followed by thrombolysis with tissue-type plasminogen activator (tPA). When thrombolysis was delayed for 3 h following embolism, neither tPA nor the tPA/ICAM combination reduced neurological damage. 

CD49 Cluster of differentiation 49 CD51 Known to be vitronectin receptor alpha chain CD54 Known to be Intercellular adhesion molecule-1 also known as ICAM-1... 

CK Creatine phosphokinase CKMB The myocardial-specific isoenzyme of creatine phosphokinase Cl The chemical symbol for chloride CL Chemiluminescent CLA Cutaneous lymphocyte antigen CL18/6 Anti-ICAM-1 monoclonal antibody... 

---