ICAM-1 receptor

The actual process of infection is not as simple as is usually believed. Most of the serotypes share a common receptor on host cells, which is an intercellular adhesion protein called ICAM-1. This is a transmembrane glycoprotein whose extracellular portion comprises several immunoglobulin domains of the IgG class. It appears that the normal role of ICAM-1 is to allow adhesion between the cell and leucocytes during injury or infection. Unwittingly, the ICAM-1 receptor has been hijacked by rhinoviruses as their receptor. Interestingly, ICAM-1 has other functions, which include sequestration of erythrocytes that have been infected by the malaria parasite Plasmodium falciparum, thus allowing them to avoid the attentions of the host s immune system. 

Bertonati, C., and Tramontano, A. (2007). A model of the complex between the PfEMPl malaria protein and the human ICAM-1 receptor. Proteins 69, 215-222. 

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. 

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

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... 

Greve JM, Davis G, Meyer AM, et al. The major human rhinovirus receptor is ICAM-1. Cell 1989 56 839-847. 

Staunton DE, Merluzzi VJ, Rothlein R, Barton R, Marlin SD, Springer TA. A cell adhesion molecule ICAM-1 is the major surface receptor for rhino-viruses. Cell 1989 56 849-853. 

K. Drickamer, and A.-C. Roche, Oligolysine-based oligosaccharide clusters selective recognition and endocytosis by the mannose receptor and dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin, /. Biol. Chem., 278 (2003) 23922-23929. 

H8. Horst, E., Meijer, C., Radaszkiewicz, T., Ossekoppele, G., Van Krieken, J., and Pals, S. T., Adhesion molecules in the prognosis of diffuse large cell lymphoma expression of a lymphocyte homing receptor (CD44), LFA-1 (CDIIa/18) and ICAM-1 (CD54). Leukaemia 4, 595-599 (1990). 

Histamine contributes to the progression of allergic-inflammatory responses by enhancement of the secretion of proinflammatory cytokines like IL-la, IL-1(3, IL-6 as well as chemokines like RANTES or IL-8, both in several cell types and local tissues [26-29]. Endothelial cells express functional HRl and HR2 and increased adhesion molecule expression such as ICAM-1, VCAM-1 and P-selectin was demonstrated by histamine infusion via HRl [30-32]. Histamine regulates the expression of its own receptors on endothelial cells and influences the overall inflammatory reaction [33]. 

In monocytes stimulated with Toll-like receptor-triggering bacterial products, histamine inhibits the production of proinflammatory IL-1-like activity, TNF-a, IL-12 and IL-18, but enhances IL-10 secretion, through HR2 stimulation [26, 69]. Histamine also downregulates CD 14 expression via Hj receptors on human monocytes [70]. The inhibitory effect of histamine via Hj receptor appears through the regulation of ICAM-1 and B7.1 expression, leading to the reduction of innate immune response stimulated by LPS [71]. 

Human rhinoviruses (HRV) are members of the Picornaviridae family. The HRVs are classified according to their receptor specificity into members of the major and minor groups. The 87 members of the major-group viruses bind to the intracellular adhesion molecule receptor 1 (ICAM-1), whereas the 12 serotypes of the minor group bind to members of the low-density lipoprotein receptor family (LDLR) [42]. Rhinoviruses cause more than a billion cases of the common cold each year and are also associated with asthma exacerbations [43,44]. Statistically, one encounters one to three infections per year on the average [45]. As a result, rhinoviral infections are responsible for 25 million days of missed work in the USA [46]. 

Platelets also express adhesion receptors of the selectin gene family (P-selectin) and of the immunoglobulin gene superfamily (PECAM-1 and ICAM-2) (6). Expression of PECAM-1 and ICAM-2 may play a role in platelet interactions with endothelial cells and leukocytes, respectively. 

The HRVs have been divided into the major and minor receptor groups based on two identified cellular receptors [3]. The major group, which is comprised of approximately 90 serotypes, binds to the intercellular adhesion molecule 1 (ICAM-1) [20]. The minor group, about 10 serotypes, binds to the low density lipoprotein receptor family [21]. 

The canyons are depressions approximately 15 to 20 A deep that encircle each icosahedral five-fold axis (Figure 1). When first seen in HRV 14, these canyons were postulated to be the site at which a cellular receptor would bind. Subsequent electron-microscopic data revealed that ICAM-1 does indeed bind in the canyon as predicted, although in a somewhat different orientation than early models [22,23]. These canyons allow the receptor binding sites to escape immunological surveillance because the canyons are too narrow to allow an immunoglobulin to contact the canyon floor. Directly underneath the floor of the canyon lies a second important structure, the VP1 hydrophobic pocket. 

This pocket is inside the P barrel of VP1, directly underneath the canyon floor where ICAM-1 binds (Figure lc). The proximity of the hydrophobic drug-binding site to the receptor-binding site explains the effects these compounds have on viral attachment in specific HRV serotypes (see below). 

Figure 7-15 (A) Schematic diagram of the icosahedral shell of a human rhinovirus showing the arrangement of the three subunits VP1, VP2, and VP3, each present as 60 copies. (B) Stereoscopic view of an image of the virus "decorated" by the binding of two immunoglobulinlike domains of the intercellular adhesion molecule ICAM-1, a natural receptor for the virus.

IL-18 also induces IL-4, IL-10 and IL-13 production, increases IgE expression on B cells and in association with IL-2, it enhances stimulus-induced IL-4 production from TH2 cells. Bone marrow-derived basophils produce IL-4 and IL-13 in response to a stimulus from IL-18 and IL-3. IL-18 in combination with IL-12 induces IFN-y from dendritic cells and bone marrow-derived macrophages. Adhesion molecules, ICAM-1 and VCAM-1, are induced by this cytokine on synovial fibroblasts and endothelial cells. It inhibits osteoclast formation via its induction of GM-CSF from T cells. The receptors ofIL-18, IL-18Ra and IL-18R(3, share their signaling mechanisms via the IL-1R family. Toll-like receptors also share the downstream signaling pathway of IL-18 and are known to regulate IL-18 expression. 

Mwatha, J.K., Kimani, G., Kamau, T., Mbugua, G.G., Ouma, J.H., Mumo, J., Fulford, A.J., Jones, F.M., Butterworth, A.E., Roberts, M.B. and Dunne, D.W. (1998) High levels of TNF, solubleTNF receptors, soluble ICAM-1 and IFN-gamma, but low levels of IL-5, are associated with hepatosplenic disease in human schistosomiasis mansoni. The Journal of Immunology 160, 1992-1999. 

Interaction of EMPs with Monocytes. As observed with other MPs, EMPs have the ability to interact with other cell types. Sabatier et al. have demonstrated that EMPs bind to both THP-1 and monocytic cells and elicit their procoagulant activity [66]. EMP binding occurred in a time- and dose-dependent manner, with a maximal effect observed at a ratio of 50 1 EMPs. This effect appeared to be dependent on ICAM-1 and beta2 integrins, as blocking these receptors resulted in a decrease of the procoagulant effect. 

Gustafson, S., Wikstreom, T., and Juhlin, L., Histochemical studies of hyaluronan and the hyaluronan receptor ICAM-1 in psoriasis, hit. J. Tissue. React., 17, 167, 1995. 

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