FOAM CELL APOPTOSIS AND THE DEVELOPMENT OF THE LIPID CORE OF HUMAN ATHEROSCLEROSIS

A characteristic feature of the advanced atherosclerotic lesion is the acellular lipid core, which appears to result at least partly from the death of macrophage foam cells. This study shows that foam cell death at the edge of the lipid core includes both necrosis and apoptosis and that remnants of apoptotic nuclei are present within the lipid core. Apoptotic cells were identified by transmission electron microscopy and by nick end-labelling using terminal deoxynucleotidyl transferase (TUNEL). Some TUNEL-positive cells also expressed proliferating cell nuclear antigen (PCNA). The cause of foam cell death in atherogenesis is unknown, but oxidized low-density lipoprotein (LDL) can cause macrophage apoptosis in vitro and might therefore play a role in the formation and enlargement of the lipid core.     

Solid-phase synthesis of phosphopeptides

We report the solid-phase synthesis of peptides containing O-phosphoserine. Coupling was with commercially available Fmoc-amino acid pentafluorophenyl esters, with base used at each cycle to cleave Fmoc. Phosphorylation of those serine residues left unprotected on the peptide-resin was achieved with dibenzylphosphochloridate, and finally trifluoroacetic acid was used to remove side-chain protecting groups (including the benzyl groups used for the phosphate), and to cleave the peptide from the resin in the same step. This synthetic strategy enables the preparation of peptides with individual, selectively phosphorylated residues. Alternative approaches to introduce protected phosphate and continue with coupling of further amino acids were less advantageous due to the lability of the phosphate group to base and to steric hindrance.     

The Detection of Iso-Antigens on Leukemic Cells Using the Cytotoxicity Test

The cytotoxicity test has been shown to give reproducible information concerning specific iso-antigens of human leukemic lymphoxytes. The distributionfrequency of these antigens is at least as great in chronic lymphocytic leukemiaantigens or of decreased cellular reactivity. The majority of patients weretested repeatedly and in most instances the cytotoxicity test remained constant,regardless of drug therapy and disease status. Cells from five patients havingacute granulocytic leukemia were typed in a similar fashion and containedantigens in common with normal lymphocytes.

Submitted on February 23, 1966 Accepted on April 15, 1966