Expression of a negative regulator of human erythropoiesis by fluidized lymphocyte plasma membranes.
Regulation of hematopoiesis by paracrine molecules occurs in vitro. In some cases, hematopoietic paracrine factors have been localized to the plasma membrane of accessory cells. We have purified a unique integral membrane glycoprotein from normal human B cells that functions in vitro as a paracrine factor whose activity is directed toward erythroid progenitor cells. This factor is also spontaneously exfoliated from the cell surface as a component of extracellular vesicles. Analysis of the lipid and protein compositions and membrane lipid order of these extracellular vesicles reveals them to be biochemically distinct and more fluid than their parent membranes. Evidence in nonhematopoietic culture systems indicates that cell membrane function may be altered by modifying membrane fluidity. In an effort to accelerate growth factor release, plasma membranes of B cells were fluidized by incubation with an emulsion of Liposin II, phosphatidylcholine, and phosphatidylethanolamine. Fluidity assessed by steady-state fluorescence polarization was reduced in lipid-treated cells. Exfoliation was 3-4-fold higher from lipid-treated cells relative to untreated cells. Unexpectedly, a negative signal for burst-forming unit-erythroid (BFU-E) proliferation was expressed in membranes, in shed extracellular vesicles, and in supernatants of medium conditioned by the fluidized cells. Purification of the inhibitor is under way. The data are consistent with the hypothesis that accessory cell plasma membranes may positively or negatively regulate erythroid differentiation, depending upon the exchange of cholesterol and phospholipids between plasma membrane and ambient lipid pools.
Dainiak
N
N
Department of Medicine, University of Connecticut Health Center, Farmington 06030.
Guha
A
A
Silva
M
M
Sorba
S
S
Armstrong
M J
MJ
D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D002455:Cell Division; D002462:Cell Membrane / Q000502:physiology; D004920:Erythropoiesis / Q000502:physiology*; D006131:Growth Inhibitors / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D008051:Lipid Bilayers; D008560:Membrane Fluidity; D008954:Models, Biological
D006131:Growth Inhibitors; D008051:Lipid Bilayers