Regulation of lipopolysaccharide-induced granulopoiesis and macrophage formation by spleen cells. I. Relationship between colony-stimulating factor release and lymphocyte activation in vitro.
Addition of bacterial lipopolysaccharide (LPS), a B cell mitogen, to mouse spleen cultures strongly stimulated production of colony-stimulating factor (CSF), the humoral regulator of granulopoiesis, and macrophage formation in vitro. Secretion of CSF from LPS-stimulated spleen cells coincided with cellualr DNA synthesis and cell transformation and both activities could be attributed to the lipid A moiety of the molecule. Different experimental approaches were used to study the relationship of CSF release and lymphocyte activation in response to LPS: a) modification of LPS with polymyxin B, an antibiotic bactericidal for most Gram-negative bacteria, caused a marked reduction in mitogenic activity, although the ability to induce CSF was not significantly altered; b)spleen cells from CBA/N mice, a mutant strain with an x-linked genetic defect in immunologic and mitogenic responses to polyclonal activators including LPS, showed diminished mitogeinc responses; however, high levels of CSF were produced; c) mitotic and DNA inhibitors (colchicine and cytosine arabinoside) did not affect CSF release although they completely inhibited mitogenicity. Thus, the spleen cell population participating in the process of LPS-induced CSF generation is probably a nondividing, terminally differentiated one without need for DNA synthesis. In addition, it was also shown that active RNA and protein synthesis are needed in this process.
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D002454:Cell Differentiation; D002455:Cell Division; D002999:Clone Cells; D003078:Colchicine / Q000494:pharmacology; D003115:Colony-Stimulating Factors / Q000378:metabolism*; D003561:Cytarabine / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D006023:Glycoproteins / Q000378:metabolism*; D006098:Granulocytes / Q000276:immunology*; D066298:In Vitro Techniques; D007700:Kinetics; D007962:Leukocytes / Q000276:immunology*; D008055:Lipids / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008934:Mitogens; D009154:Mutation; D011113:Polymyxins / Q000494:pharmacology; D011135:Polysaccharides, Bacterial / Q000494:pharmacology; D013154:Spleen / Q000276:immunology* / Q000378:metabolism
D000963:Antimetabolites; D003115:Colony-Stimulating Factors; D006023:Glycoproteins; D008055:Lipids; D008070:Lipopolysaccharides; D008934:Mitogens; D011113:Polymyxins; D011135:Polysaccharides, Bacterial; D003561:Cytarabine; D004247:DNA; D003078:Colchicine