Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Using tissue cell culture to make a protein or polypeptide
Patent
1996-05-02
2000-02-22
Schwadron, Ronald B.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Using tissue cell culture to make a protein or polypeptide
435 702, 435332334, 435343, 435344, 436548, 5303871, 5303873, 53038722, 5303887, 530809, 5303888, C07K 1628, C07K 1630, C07N 512, C07N 502
Patent
active
060279222
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to new in vitro generated human foam cells, the method for preparing the same, the use of said foam cells in an in vitro method for selecting specific compounds, more particularly monoclonal antibodies found to recognize specifically ICAM-3, a process for preparing the monoclonal antibodies according to the invention, and their use for pharmaceutical and diagnostic purposes.
Atherosclerosis involves a combination of changes in the intima of the arterial wall, resulting in thickening and hardening of the arteries; typical lesions such as fatty streaks and fibrous plaques consisting of lipids, proteins and other components become calcified fibrous plaques which affect the underlying media at later stages. The disease originates from a response to an injury of the endothelial cells and has a lot of properties in common with inflammatory processes in other tissues (Ross, 1986).
Key elements of the atherosclerotic plaque are the foam cells, which are mainly derived from circulating blood monocytes. Upon entering the arterial wall, monocytes differentiate into macrophages that avidly take up large amounts of modified lipoproteins, hence resulting in foam cell formation. The injuries of the arterial lumen lead to occluded blood flow and ultimately to clinical complications such as myocard infarct, stroke, thrombosis, angina, renal hypertension and peripheral vessel diseases.
Early detection of atherosclerotic plaques is of primarily importance to allow a timely intervention to reduce plaque size and formation and to prevent new plaque formation. Arteriography is conventionally used for diagnosing advanced vascular diseases. Because of the risks resulting from this catheterization procedure, arteriography is only performed on patients with advanced or acute atherosclerotic disease. Until now, no diagnostic methods exist that permit an early detection of atherosclerotic plaques, and there is a need for better non-invasive techniques and reagents capable of detecting, mapping and treating early, non-stenosing, non-flow-disturbing arterial lesions.
Kodama et al. (WO 90/05748) have characterized a scavenger receptor molecule and antibodies against this receptor for the detection and treatment of atherosclerosis. It concerns a receptor protein of about 220 kDa that binds acetylated and oxidized LDL. In order to isolate this receptor PMA differentiated THP-1 cells were used.
Multiple models for the generation of in vitro foam cells are already described for murine cell lines, where one of the classical systems consists of incubating murine J774A.1 cells with acetylated low density lipoproteins (LDL) for 48 hours, resulting in an intracellular cholesterol content of >100 .mu.g/mg cell protein and a degree of esterification of +50% (Tabas et al., 1985; Via et al., 1985; Snow et al., 1988; 1992). In contrast, human macrophage-like cell lines HL-60 and U-937 could not be transformed into foam cells using acetylated-LDL (Via et al., 1985). Previous induction with phorbol 12-myristate 13-acetate (PMA) or conditioned medium of concanavalin A-stimulated lymphocytes did not influence their acetyl-LDL metabolism. The human monocytic cell line THP-1 (Tsuchiya et al., 1980) could be induced by PMA to a differentiated phenotype expressing numerous functional macrophage characteristics (Tsuchiya et al., 1982). The suspension cells became growth arrested and adherent to the substrate, and secreted lipoprotein lipase and apolipoprotein E (Tajima et al., 1985; Auwerx et al., 1988; Menju et al., 1989). Hara et al. (1987) described an increased degradation of acetyl-LDL in PMA-differentiated THP-1 cells, even though a total cholesterol accumulation of +45 .mu.g/mg cell protein after 48 hours is rather low in comparison to the observed cholesterol content of foam cells isolated from the atherosclerotic plaque, which normally ranges up to 300 .mu.g/mg protein (Haley et al., 1977; St. Clair, 1986). Also, in a study of Yamamoto et al. (1988) involving PMA-induced human THP-1 and UE-12 cells, generated foam cel
REFERENCES:
Harris et al., TIBTECH, 11:42-44, 1993.
Waldmann, Science, 252:1657-1662, 1991.
ATCC Cell lines and hybridomal catalogue, 8th Edition, 1994, pp. 339, XV and XVI.
Borrebaeck et al., Imm. Today, 14: 477-479, 1993.
Schlossman et al., "Leucocyte Typing V, White Cell Differentiation Antigens, Proceedings of the Fifth Int. Workshop and Conference Held in Boston, USA Nov. 3-7, 1993". Oxford Univ. Press, 1995 pp. 1457-1467.
Hani et al., Arth. and Rheuma., 37:846-854, 1994 (Abstract thereof).
Springer et al., "AS1 Adhesion structutes: section report", from "Leucocyte Typing V" ed. Schlossman et al., Oxford Univ. Press, 1995, pp. 1443-1447.
Tissue Antigens, vol. 42, No. 4, Oct. 1993, Copenhagen, p. 412, Union et al, `Up-regulation of the CD36 and Cdw17 antigen on "in vitro" human foam cells`.
Journal of Biological Chemistry, vol. 268, No. 16, Jun. 5, 1993, Baltimore, Md., U.S., pp. 11811 011816, Endemann, G. Et al `CD36 is a receptor for oxidized low density lipoprotein`.
Biochemistry vol. 27, 1988, Easton, Pa., U.S., pp. 2651-2655, Auwerx, J. H. Et al `transcriptional activation of the lipoprotein lipase and apolipoprotein E genes accompanies differentiation in some human macrophage-like cells`.
De Smet Walter
Union Ann
Innogenetics N.V.
Schwadron Ronald B.
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