Effect of hypercholesterolemia on the in vitro production of granulocytes and monocytes in the chick

Abstract

Normal and hypercholesterolemic sera were not different with regard to the number of granulocyte-monocyte clones supported or to the percentage of granulocytic clones supported. However, 97% of the mononuclear cell clones induced by hypercholesterolemic serum contained cells which had differentiated into very large, highly vacuolated macrophages (= giant cell) of very low replicative potential (clone size = 3–9 cells). When low-density lipoproteins isolated from hypercholesterolemic plasma (LDL-H) were added to cultures stimulated with normal serum, most (74%) of the resulting clones were giant-cell ones. Other classes of lipoproteins had this effect but the magnitude was lower (53% maximum). Even LDL from normal animals was ineffective. Approximately 70% of the mononuclear cell clones induced by normal serum contained cells which had differentiated into monocytes and small macrophages (three to four times smaller than giant cells) of very high replicative potential (clones ⩾ 50 cells). The number of granulocytic clones was not affected by any lipoprotein class. Dilution, heat inactivation, and lipoprotein depletion of hypercholesterolemic serum eliminated its ability to induce giant cells and, following these treatments, it was as active (or more in the case of lipoprotein depletion) as normal serum at inducing regular macrophage clones. These treatments showed that a decrease in a serum's ability to induce giant cells was correlated in degree and kinetics with an increase in its ability to produce regular macrophages, suggesting that the two cell types derive from a common progenitor.