Intercellular adhesion molecule function

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. 

Diacovo TG, Defougerolles AR, Bainton DF, Springer TA. A functional integrin ligand on the surface of platelets-intercellular-adhesion molecule-2. J Clin Invest 1994 94 1243-1251. 

Rat kidneys were perfused ex situ with phosphorothioate intercellular adhesion molecule (ICAM)-l AS-ODN and exposed to 30 min cold or warm ischaemia. After this time the kidneys were transplanted to syngeneic nephrectomized rats. Treatment with 10 mg antisense reduced the harmful effect of transplantation on renal function [132]... 

Selected adhesion molecules represent yet another antibody target. Adhesion molecules, such as LFA-1 (leukocyte function-associated antigen-1) and ICAM-1 (intercellular adhesion molecule 1), play central roles in promoting migration of inflammatory cells to the sites of damage. Such activities underlie many of the symptoms of conditions such as rheumatoid arthritis. Inhibition of adhesion molecule function by administration of antibodies raised against them may, therefore, demonstrate therapeutic potential in some instances. 

Marlin, S. D. and Springer, T. A. (1987). Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1). Cell 51, 813-819. 

The quaternization method is also highlighted by the short asymmetric synthesis of cell adhesion molecule BIRT-377 (Scheme 5.24), which is a potent inhibitor of the interaction between intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) [16]. Thus, asymmetricp-bromobenzylation of the alanine derivative 42 (R1 = Me) with (S)-18 under similar phase-transfer conditions as described above gave rise to p-bromobenzylalanine ester 10 in 97% ee (83% yield). A similar asymmetric p-bromobenzylation of alanine ethyl ester 42 (R1 = Me, R= Et) gave the amino ester 47 (R= Et) in 90% ee (86% yield). The amino ester 47 (R = t-Bu or Et) was treated with 3,5-dichlorophenyl isocyanate in the presence of sodium carbonate in dimethylsulfoxide (DMSO) to furnish the hydantoin 48 in 86%... 

Nakayama, H., Sano, H., Nishimura, T., Yoshidi, S., and Iwamoto, I. (1994) Role of vascular cell adhesion molecule 1/very late activation antigen 4 and intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 interactions in antigen-induced eosinophil and T cell recruitment into the tissue. J. Exp. Med. 179,1145-1154. 

Casasnovas, J., Pieroni, C., and Springer, T. A. (1999). Lymphocyte function-associated antigen-1 binding residues in intercellular adhesion molecule-2 (ICAM-2) and the integrin binding surface in the ICAM subfamily. Proc. Natl. Acad. Sci. USA 96, 3017-3022. 

During the generation of functional lymphoid tissue organizers, LT-pR signaling leads to expression of mucosal addressin cell adhesion molecule (MAdCAM-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cell-adhesion molecule 1 (VCAM-1) on endothelial cells, as well as the production of the chemokines CXCL13, CCL19, and CCL21 by stromal cells and HEVs (Carlsen et al., 2005). 

BIRT-377 (1), a small molecule inhibitor of lymphocyte function-associated antigen 1 (LFA-1), was first discovered by Kelly and coworkers in 1999. It was shown to have potential therapeutic utility in the treatment of a variety of inflammatory and immune disorders. In binding to intercellular adhesion molecules, the cell-surface receptor LFA-1 allows many cell-cell adhesion events that control immunological functions. A lack of these synaptic functions leads to potentially life-threatening immunodeficiency diseases. In case of overactive immune responses, an LFA-1 inhibitor can be used to attenuate the inflammatory responses. These immunosuppressive activities have been tested in vitro, and early clinical trials on transplantation have already been undertaken. ... 

It seems likely that MBP exerts some efiects on epithelial function at much lower concentrations than those required to produce cellular dysfunction and detachment. Over a 24 h exposure period human nasal epithelium showed a 50% u[)-regulation of intercellular adhesion molecule-1 (ICAM-1) expression when exposed to concentrations of MBP within the range 0.1—0.2 ftgmP (Ayars et al., 1991). 

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