Intercellular cell adhesion molecule

Losartan was shown to increase uric acid excretion by inhibiting its tubular reabsorption. This effect does not lie within the spectrum of the blockade of AT, receptors, but rather is a genuine action of the drug on renal tubuli. Losartan was also shown to decrease ocular pressure in normotensive as well as in hypertensive patients with or without glaucoma. Losartan and eprosartan also reduce central sympathetic tone. A metabolite of losartan, EXP-3179 (Fig. 5.8), does not block AT, receptors but may inhibit the atherosclerotic process by suppressing intercellular cell adhesion molecules (ICAM-1), cyclooxygenase-2 (COX-2) and thrombox-ane-A2 (TXA-2). These effects of losartan may lead to potential indications other than blood pressure reduction in hypertensive patients [7]. 

FPPS farnesyl pyrophosphate synthase ICAM intercellular cell adhesion molecule... 

Ali, S., J. Kaur, and K. D. Patel. 2000. Intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and regulated on activation normal T cell expressed and secreted are expressed by human breast carcinoma cells and support eosinophil adhesion and activation. Am J Pathol 157 313. 

Figure 1. Interaction between leukocytes and endothelial cells of Mood vessels (modified from [3e]). Top overview bottom single steps with explanation of the symbols. Stimulation of endothelial cells by various mediators and factors leads to the expression of selectins and platelet-activating factor (PAF). The extravasation of leukocytes from the postcapillary venules starts with a weak, low-affinity, selectin-mediated adhesion of the leukocytes to endothelial cells, which leads to a slowing down of the leukocyte velocity (rolling). In the second phase a PAF-mediated activation of the leukocyte integrins occurs. In the third phase the activated integrins bind with high affinity to their ligands which are located on the endothelial cell surface. These ligands are called intercellular cell adhesion molecules (ICAM) and are members of the immunoglobulin superfamily. The firm adhesion of the leukocyte cells to the endothelium and finally their departure from the blood vessel (extravasation) results.

Hulthe J, Wikstrand J, Mattsson-Hulten L, Fagerberg B. Circulating ICAM-1 (intercellular cell-adhesion molecule 1) is associated with early stages of atherosclerosis development and with inflammatory cytokines in healthy 58-year-old men the Atherosclerosis and Insulin Resistance (AIR) study. Clin Sci 2002 103 123-129. 

IkB inhibitory protein kappa B lCAM-1 intercellular adhesion molecule 1 lL-1 interleukin-1 LDL low density lipoprotein MAPKs mitogen activated protein kinases MCP-1 macrophage chemotactic protein 1 M-CSF macrophage colony stimulating factor mmLDL minimally modified LDL NAC A-acetylcysteine NF-kB nuclear factor-kappa B oxLDL oxidised LDL PKC protein kinase C PMA phobol myristate acetate ROS reactive oxygen species TNF-a tumour necrosis factor alpha AM-1 vascular cell adhesion molecule 1... 

Haraldsen, G., Kvale, D., Lien, B., Farstad, I.N. and Brandtzaeg, P. (1996) Cytokine-regulated expression of E-selectin, intercellular adhesion molecule-1 (IGAM-1), and vascular cell adhesion molecule-1 (VGAM-1) in human microvascular endothelial cells. Journal of Immunology 156, 2558-2565. 

Ohashi Y, Nakai Y, Sakamoto H, Ohno Y, Sugiura Y, Okamoto H, Tanaka A, Kakinoki Y, Kishimoto K, Hayashi M Serum levels of soluble interleukin-2 receptor in patients with perennial allergic rhinitis before and after immunotherapy. Ann Allergy Asthma Immunol 1996 77 203-208. Ohashi Y, Nakai Y, Tanaka A, Kakinoki Y, Washio Y, Kato A, Masamoto T, Sakamoto H, Yamada K Ten-year follow-up study of allergen-specific immunoglobulin E and immunoglobulin G4, soluble interleukin-2 receptor, interleukin-4, soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 in serum of patients on immunotherapy for perennial allergic rhinitis. Scand J Immunol 1998 47 167-178. 

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%... 

Other groups have emphasized that previous infections are an independent risk factor for acute stroke. This phenomenon might be at least in part attributable to the activation of cytokines and adhesion molecules such as the vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM) (5). 

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. 

---