Normal and Tumor-Bearing Host Splenic Macrophage Responses to Lipopolysaccharide

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Abstract
Lipopolysaccharide (LPS) was used to assess the responses of normal and tumor-bearing host (TBH) macrophages (Mπ) to activation signals. Mπ were incubated with LPS for either 3 hr or 24 hr and then assayed for phenotypic, functional, or cell-cycle changes. A 3-hr LPS treatment had no significant effect on Mπ phenotype. In contrast, the 24-hr LPS treatment caused a significant decrease in the percentage of normal host Mac+ and Ia+ Mπ. In the TBH, a 24-hr LPS treatment caused an increase in the percentage of Mac-1+ and -2+ Mπ and a decrease in the percentage of Mac-3+ and Ia+ Mπ. When normal host Mπ were plated for 24 hr (control), there was an increase in Mac-1+ and -2+ Mπ and a decrease in Ia+ Mπ. The 24-hr TBH control showed a decrease in Mac-1+ and Ia+ Mπ. To assess functional changes, LPS-treated normal and TBH Mπ were added to the allogeneic mixed lymphocyte reaction (MLR) or the autologous MLR (AMLR). There were no significant differences in Mπ accessory activity after a 3-hr LPS treatment. A 24-hr LPS treatment of normal host Mπ also had no effect. A 24-hr LPS treatment of TBH Mπ led to a significant decrease in allogeneic T-cell reactivity, and even the 24-hr TBH control showed significant suppression of T-cell responsiveness. In the AMLR, a measure of autoreactive T-cell responsiveness, a 3-hr LPS treatment had no affect on normal host Mπ but led to increased accessory ability in TBH Mπ. TBH Mπ, however, were still less than 50% as responsive as normal host Mπ even after LPS treatment. The 24-hr LPS treatment caused a significant decrease in normal or TBH Mπ accessory activity. A 24-hr plating of normal host Mπ decreased their accessory ability. In addition to the phenotypic and functional changes after LPS treatment, Mπ cell-cycle kinetics were also investigated. The percentages of normal host Mπ in G0/G1 were not changed significantly after a 3-hr LPS treatment. In contrast, Mπ plated for 24 hr with or without LPS had a decreased percentage of cells in G0/G1. Normal host Mπ showed little change in total RNA levels after a 3-hr treatment but had increased RNA levels after a 24-hr treatment. The percentages of TBH Mπ in G0/G1 increased after a 3-hr LPS treatment. Mπ treated with or without LPS for 24 hr had a decreased percentage of cells in G0/G1. There was no change in RNA levels in TBH Mπ after a 3-hr treatment but increased levels were observed after a 24-hr treatment. The results suggest that normal and TBH Mπ respond to activating signals differently and may pinpoint functional abnormalities in TBH Mπ.