Summary
In vitro studies indicate that oxidatively modified low-density lipoprotein (oxLDL) promotes leukocyte sticking to the vascular endothelium, a constant feature of early atherogenesis. Using intravital fluorescence microscopy in the dorsal skinfold chamber model in hamsters, we investigated whether systemic administration of human LDL, oxidized by Cu2+, elicited leukocyte/endothelium interaction in vivo. While no effect was seen after injection of native LDL, oxLDL administration resulted in an immediate induction of leukocyte rolling along the microvascular endothelium and subsequent firm sticking to the wall of postcapillary venules as well as arterioles. The presented model may provide an alternative experimental approach to long-term feeding studies with atherogenic diets for the in vivo investigation of leukocyte/endothelium interaction in early atherogenesis.
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References
Berliner JA, Territo MC, Sevenian A, Ramin S, Kim JA, Bamshad B, Esterson M, Fogelman AM (1990) Minimally modified low density lipoprotein stimulates monocyte endothelial interactions. J Clin Invest 85:1260–1266
Dahlén SE, Björk J, Hedqvist P, Arfors KE, Hammarström S, Lindgren JA Samuelsson B (1981) Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: in vivo effects with relevance to the acute inflammatory response. Proc Natl Acad Sci USA 78:3887–3891
Endrich B, Asaishi K, Goetz A, Messmer K (1980) Technical report—a new chamber technique for microvascular studies in unanesthetized hamsters. Res Exp Med 177:125–134
Fagiotto A, Ross R, Harker L (1984) Studies of hypercholesterolemia in the nonhuman primate: I. Changes that lead to fatty streak formation. Arteriosclerosis 4:323–340
Ford-Hutchinson AW, Bray MA, Doig MV, Shipley ME, Smith MJH (1980) Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature 286:264–265
Frostegard J, Nilsson J, Haegerstrand A, Hamsten A, Wigzell H, Gidlund M (1990) Oxidized low density lipoprotein induces differentiation and adhesion of human monocytes and the monocytic cell line U937. Proc Natl Acad Sci USA 87:904–908
Gerrity RG (1981) The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions. Am J Pathol 103:181–190
Grant L (1973) The sticking and emigration of white blood cells in inflammation. In: Zweifach BW, Grant L, McClumsek RT (eds) The inflammatory process, vol 2. Academic Press, New York, pp 205–249
Halliwell B, Gutteridge JMC (1989) Lipid peroxidation: a radical chain reaction. In: Halliwell B, Gutteridge JMC (eds) Free radicals in biology and medicine, vol 2. Clarendon Press, Oxford, pp 188–276
Joris I, Zand T, Nunnari JJ, Krolikowski FJ, Majno G (1983) Studies on the pathogenesis of atherosclerosis: I. Adhesion and emigration of mononuclear cells in the aorta of hypercholesterolemic rats. Am J Pathol 133:341–358
Masuda J, Ross R (1990) Atherogenesis during low level hypercholesterolemia in the nonhuman primate I. Fatty streak formation. Arteriosclerosis 10:164–177
Ohkubo C, Asano M (1988) Decubital ulcers of pads induced by hyperlipidemia in the rabbit. In: Manabe H, Zweifach BW, Meßmer K (eds) Microcirculation in circulatory disorders. Springer, Tokyo, pp 401–408
Palinski W, Rosenfeld ME, Ylä-Herttuala S, Gurtner GC, Socher SS, Bulter SW, Parthasarathy S, Carew TE, Steinberg D (1989) Low density lipoprotein undergoes oxidative modification in vivo. Proc Natl Acad Sci USA 86:1372–1376
Quinn MT, Parthasarathy S, Steinberg D (1988) Lysophosphatidylcholine: a chemotactic factor for human monocytes and its potential role in atherogenesis. Proc Natl Acad Sci USA 85:2805–2809
Redgrave TG, Roberts DCK, West CE (1975) Separation of plasma lipoproteins by density-gradient ultracentrifugation. Anal Biochem 65:42–49
Ross R (1986) The pathogenesis of atherosclerosis—an update. N Engl J Med 314:488–500
Sparrow CP, Parthasarathy S, Steinberg D (1989) A macrophage receptor that recognizes oxidized low density lipoprotein but not acetylated low density lipoprotein. J Biol Chem 264:2599–2604
Steinberg D, Parthasarathy S, Carew TE, Witztum JL (1989) Beyond cholesterol. N Engl J Med 320:915–924
Steinbrecher UP, Parthasarathy S, Leake DS, Witztum JL, Steinberg D (1984) Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci USA 81:3883–3887
Watanabe T, Hirata M, Yoshikawa Y, Nagafuchi Y, Toyoshima H, Watanabe T (1985) Role of macrophages in atherosclerosis: sequential observations of cholesterol-induced rabbit aorta lesion by the immunoperoxidase technique using monoclonal antimacrophage antibody. Lab Invest 53:80–90
Zeintl H, Sack FU, Intaglietta M, Meßmer K (1989) Computer assisted leukocyte adhesion measurement in intravital microscopy. Int J Microcirc [Clin Exp] 8:293–302
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Lehr, H.A., Hübner, C., Nolte, D. et al. Oxidatively modified human low-density lipoprotein stimulates leukocyte adherence to the microvascular endothelium in vivo. Res. Exp. Med. 191, 85–90 (1991). https://doi.org/10.1007/BF02576662
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DOI: https://doi.org/10.1007/BF02576662