No abstract

ABSTRACT

The Schwann cells in maturing neuroblastomas differ genetically from the neuronal cells. The normal number of chromosomes in Schwann cells and the abnormal number in neuroblastic ganglionic cells suggests that Schwann cells are a reactive population of normal cells that invade the neuroblastoma. Near-trip-loidy of neuroblastoma cells and intact chromosome 1 are presumably genetic prerequisites for spontaneous organoid maturation, because we found no diploidy or chromosome 1 depletions in the neuronal cells of spontaneously maturing neuroblastomas.

Incubation of low density lipoprotein (LDL) with endothelial cells or smooth muscle cells overnight has resulted in an oxtdative modification of LDL that results in its recognition by macrophages by way of the acetyl LDL receptor. In the present study, we examined whether macrophages themselves can oxidize and modify LDL in a manner similar to that of endothelial cells. Incubation of 125 l-labeled LDL with resident or thioglycollate-elicited macrophages for 24 hours in Ham's F-10 medium resulted in the appearance of thiobarbituric acid (TBA) reactive materials and trichloroacetic acid (TCA) soluble radioactivity in the medium. The LDL harvested from these incubations showed increased electrophoretic mobility and was degraded rapidly when added to fresh macrophages as compared to LDL previously incubated in the absence of cells. T he accumulation of lipid-laden foam cells of monocvte origin in the aortic intima is an early event in the development of atherosclerosis.1 " 3 Monocyte-macrophages take up and degrade native low density lipoprotein (LDL) by way of the classical LDL (B/E) receptor, but only at rather low rates. 4 On the other hand, chemically acetylated LDL and other chemically modified forms of LDL 5 -6 are taken up much more rapidly by a distinct, alternative receptor, designated the acetyl LDL or scavenger receptor. 7Incubation of macrophages with these chemically modified forms readily generates foam cells whereas it is difficult to generate foam cells by incubation with native LDL 4 unless very long incubation times are used.8 Incubation of native LDL overnight with cultured endothelial cells has been shown to result in a modification that converts LDL to a form recognized by the same receptor that recognizes acetyl LDL.9 " 11 This modification has been shown to depend upon the presence of trace metals in the medium, to involve extensive lipid peroxidation, and to require the ac- tion of a phospholipase A 2 . 12 ' 13 The peroxidation of LDL lipids during such incubations has been shown to account for the cytotoxicity of LDL for cultured endothelial cells. 14 All of these changes can be blocked by the addition of alpha-tocopherol, butylated hydroxytoluene (BHT), or by probucol, a drug used in the management of hyperlipoproteinemia. 15 Since macrophages generate active oxygen species, which may play a role in their ability to scavenge and kill cells, it seemed likely that they might share the ability to oxidatively modify LDL. It was recently reported 16 ' 17 that LDL is oxidized by human monocytes and neutrophils and that the electrophoretic mobility of LDL is increased after incubation with cultured porcine monocytes. We report here that mouse peritoneal macrophages, like circulating human monocytes, can cause extensive oxidation of LDL lipids. We show further that the modified LDL is specifically recognized by the acetyl LDL receptor on the same cells that oxidized the LDL and, finally, that this macrophage-modified LDL competes with endothelial cellmodified LDL for uptake and degradation.

Leukaemic stem cells in patients with CD33(+) AML express CD33. This observation is in favour of novel treatment concepts employing CD33-targeting antibodies in AML.