Serum lipoprotein inhibitors of granulopoiesis in human bone marrow cultures.

Ammonium sulphate fractionation of human serum showed that two fractions contained an inhibitor of cluster and colony formation in agar cultures of human bone marrow cells. Further investigations demonstrated this inhibition to be caused by lipoproteins. When freshly prepared, only light density lipoproteins (LDL) were found to be inhibitory. During storage, very light density lipoproteins (VLDL) acquired inhibitory activity, while high density lipoproteins (HDL) did not show any inhibition of human bone marrow cultures. The possibility of toxic degradation of lipoproteins as an explanation for the inhibition was investigated by preincubation of human marrow cells with lipoproteins for 6 hours (37 degrees C) after storage of the lipoproteins under nitrogen (4 degrees C) for various intervals up to 48 days. Preincubation was found to be non-toxic (viable cell counts) and without colony/cluster-reducing ability for incubated marrow cells compared to controls. Addition of lipoproteins to mouse marrow cells and Ehrlich ascites tumour cells resulted in no change in colony formation by Ehrlich cells, whereas mouse marrow cells were inhibited, but to a lesser degree than human marrow cells.