Macrophage activation for tumor cytotoxicity: Control of macrophage tumoricidal capacity by the LPS gene

L. P. Ruco, M. S. Meltzer, D. L. Rosenstreich

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

In contrast to cells from C3H/HeN mice, macrophages from LPS-unresponsive C3H/HeJ mice fail to develop tumoricidal capacity after a variety of in vivo or in vitro activation stimuli. The macrophage-tumoricidal defect of C3H/HeJ mice was evident with treatments not dependent upon exogenously added LPS: BCG infection, T cell mitogens, or in vitro exposure to lymphokines. This study was designed to determine if macrophage-tumoricidal capacity was controlled by the LPS gene. Tumoricidal responses of macrophages from BCG-infected F1 hybrids (C3H/HeJ x C3H/HeN) were intermediate to those of the parental strains. There were no differences in cytotoxic responses between macrophages from BCG-infected male or female F1 hybrids. These responses suggest an autosomal codominant pattern of inheritance for control of macrophage cytotoxicity similar to that previously reported for B cell responsiveness to LPS. In a backcross linkage analysis (C3H/HeJ x F1), there was complete concordance in the expression of macrophage-tumoricidal capacity and spleen cell capacity to proliferate in response to LPS. Furthermore, macrophage-tumoricidal capacity correlated with LPS responsiveness in other inbred mouse strains. Macrophages from BCG-infected, LPS-unresponsive C57BL/10ScCR mice were not tumoricidal in vitro, whereas cells from BCG-infected, LPS-responsive C57BL/10Sn mice were. Moreover, analysis of tumoricidal responses in eight different BXH recombinant inbred strains of mice revealed that the development of cytotoxic macrophages during BCG infection was associated with the capacity of each strain to respond to LPS. These findings strongly suggest that the gene for control of macrophage-tumoricidal capacity is either closely linked or identical to the LPS gene.

Original languageEnglish (US)
Pages (from-to)543-548
Number of pages6
JournalJournal of Immunology
Volume121
Issue number2
StatePublished - Dec 1 1978
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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