Lymphocyte function-associated interactions

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. 

Nickoloff BJ, Mitra RS, Green J, Zheng XG, Shimizu Y, Thompson C, Turka LA Accessory cell function of keratinocytes for superantigens. Dependence on lymphocyte function-associated antigen-l/intercellular adhesion molecule-1 interaction. J Immunol 1993 150 2148-2159. 

ICAM-1 and lymphocyte function-associated protein (LFA)-l pathway are involved in monocyte-endothelium interaction during a cholesterol-rich diet. In rats on high-cholesterol diet, ICAM-1 expression was increased on aortic EC, which was associated with increased monocyte adherence (more than 85% of adherent macrophages exhibited LFA-1 antigen and injecting the animals with ICAM-1 monoclonal antibody and LFA-1 monoclonal antibody reduced mostly LFA-1 positive macrophages) (167). In clinically healthy middle-aged men, levels of soluble ICAM-1 (sICAM-1), but not sVCAM-1 or E-selectin, were associated with subclinical atherosclerosis and inflammatory variables (168). 

CJ-Receptors are localized ia the brain stem and limbic stmcture, regions associated with endocrine function (76). In the periphery, CJ-receptors are found in the Hver, heart, ileum, vas deferens, and on lymphocytes and thymocytes. Although there is insufficient evidence to clearly define the functional role of CNS CJ-sites, based on the effects of PCP and the interaction of haloperidol with CJ-sites, CJ-receptor ligands may be antipsychotics or used for the treatment of substance abuse. Several CJ-receptor ligands have shown neuroprotective effects in vivo. Ifenprodil (315) and CNS 1102 (316) are being developed for treatment of stroke (Table 18). 

A characteristic that significantly differentiates some of the cytokines from other hormones is the coupling of their activity to cell-cell interactions. The function of some cytokines such as the interleukins lL-4, lL-5, lL-6 and lL-10 is closely associated with the interaction between B and T lymphocytes. 

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