Restoration of the lipopolysaccharide-responsive phenotype in C3H/HeJ peritoneal macrophage-P388D1 cell hybrids.
The fusion of thioglycollate-elicited peritoneal macrophages from the lipopolysaccharide (LPS)-nonresponsive C3H/HeJ mouse strain to a hypoxanthine phosphoribosyltransferase (HPRT)-negative variant of the murine macrophage cell line P388D1 has resulted in the derivation of eight hybrid clones following HAT selection. Propidium-Iodide staining followed by flow cytometry has demonstrated that the DNA content of the hybrids represents the sum of the parents. Codominant expression of class I antigens from both parental haplotypes is observed in the hybrids. While class II antigens are inducible following a 72-hr induction with gamma interferon-containing supernatants, the amount of each haplotype varies between clones. These hybrids demonstrate Fc-mediated erythrophagocytosis in contrast to P388D1. In distinction to the C3H/HeJ primary peritoneal-macrophage parent, LPS treatment of the hybrids results in the increased release of both interleukin-1 (IL-1) and cachectin/tumor necrosis factor (TNF) into culture supernatants. Therefore, cell fusion has resulted in the stable restoration of the LPS-responsive phenotype in C3H/HeJ macrophage hybrids. These macrophage hybrids should serve as useful models in understanding the regulation of macrophage effector functions in response to environmental stimuli.
Zuckerman
S H
SH
Department of Immunology, Lilly Research Laboratories, Indianapolis, Indiana 46285.
Surprenant
Y M
YM
Carlson
D G
DG
Beutler
B
B
D000818:Animals; D006680:HLA Antigens / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006822:Hybrid Cells; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D010529:Peritoneal Cavity / Q000166:cytology; D010587:Phagocytosis; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha