Isolation and characterization of three inhibitors of thymidine incorporation into bovine fetal liver cells.
During the isolation and purification of erythroid cell-stimulating factors from fetal tissues and blood, we found that they were almost invariably contaminated with substances that inhibited thymidine incorporation into erythroid cells of fetal bovine liver. We have isolated and partially sequenced three of these inhibitory factors. The first one was a 46-kDa heparin-binding protein from fetal bovine serum with 80% sequence identity with human apolipoprotein H (apo H). Although human apo H had no inhibitory activity on thymidine incorporation, the bovine apo H-like protein inhibited thymidine incorporation with an ID50 of 36 nM. It probably belongs to a group of heparin-binding apolipoproteins such as apo B and E, which have been reported to inhibit hematopoietic cells. The second inhibitor isolated from fetal bovine serum was clearly cytotoxic at a concentration of 1 nM. This 11-kDa peptide seems to be structurally related to the anaphylatoxins. The third inhibitor was isolated from human fetal intestine. The amino-terminal sequence of this protein was nearly identical to the amino-terminal sequence of human phospholipase A2 isolated from pancreas or lung. Bovine liver erythroid cell membranes are particularly sensitive to phospholipases. Since the synthesis and secretion of phospholipase A2 has been reported to be under the control of interleukin-1 or tumor necrosis factor in different cells, it is possible that this enzyme may be secreted locally and play an important role in tissue remodeling during injury or fetal development.
Li
Q G
QG
Endocrine Laboratory, Royal Victoria Hospital, Montreal, Canada.
Congote
L F
LF
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002460:Cell Line; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D004920:Erythropoiesis; D005333:Fetus; D006023:Glycoproteins / Q000097:blood / Q000302:isolation & purification; D006131:Growth Inhibitors / Q000097:blood / Q000302:isolation & purification* / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000502:physiology*; D008555:Melitten / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000494:pharmacology / Q000502:physiology; D054467:Phospholipases A2; D013936:Thymidine / Q000378:metabolism*; D053482:beta 2-Glycoprotein I
D006023:Glycoproteins; D006131:Growth Inhibitors; D053482:beta 2-Glycoprotein I; D008555:Melitten; D010741:Phospholipases A; D054467:Phospholipases A2; D013936:Thymidine