NORMAL AND TUMOR-BEARING HOST MACROPHAGE RESPONSES - VARIABILITY IN ACCESSORY FUNCTION, SURFACE-MARKERS, AND CELL-CYCLE KINETICS

Normal and tumor-bearing host (TBH) peritoneal macrophage (Mø) responses to in vitro lipopolysaccharide (LPS) treatment were measured by assessing functional and phenotypic changes. Both normal and TBH untreated Mø suppressed mixed lymphocyte reaction (MLR) reactivity at all concentrations. Normal host Mø treated with LPS for 3 h were suppressive at all concentrations. TBH Mø treated with LPS for 3 h were not suppressive in the MLR until more than 5% were added. Surprisingly, 24 h treatment of normal and TBH Mø with LPS induced cells that significantly enhanced MLR reactivity when added at 2% or 5%. These cells were not suppressive until 20% Mø concentration was reached. LPS treatment of normal and TBH Mø changed the percentage of cells expressing the surface markers Mac-1, -2, -3, and Ia as determined by flow cytometry. Normal host peritoneal Mø treated with LPS for 3 h had decreased Mac-1 and -3 expression, but there was no change in Mac-2 or Ia. Plating for 24 h did not change the percentage of Mø expressing Mac-1, -3, or Ia but did cause an increase in Mac-2+, Mø. Treatment of normal host Mø with LPS for 24 h led to a decrease in Mac-1+ and Ia+ Mø, no change in Mac-3+ Mø, but an increase in Mac-2+ Mø. LPS treatment of TBH Mø for 3 h decreased the number of Mac-1+ Mø, but Mac-2+, -3+, or Ia+ Mø numbers did not change. Plating TBH Mø for 24 h caused a decrease in the number of Mac-1+ Mø, no change in Mac-3+ or Ia+ Mø, but an increase in Mac-2+ Mø. Treatment with LPS for 24 h led to no change in the number of Mac-1+. -3+, or Ia+ TBH Mø, but Mac-2+ Mø increased. The phenotypic and functional change after LPS treatment led us to ask if these change were detectable at the level of DNA and RNA. Flow cytometric analysis of acridine orange-stained Mø was used to measure DNA and RNA levels. This analysis determines Mø cell-cycle kinetics and estimates thier RNA synthesis. In normal host Mø, a 3-h LPS treatment caused a decrease of cells in G0/G1 but an insignificant change in RNA levels. The same LPS treatment of TBH Mø caused an increase of cells in G0/G1 and a decrease in the RNA levels. The results suggest that normal and TBHMø respond to in vitro signals differently. These difference suggest that abnormal TBH Mø responses to in vivo signals may lead a tumor-induced suppression. © 1990.