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Comparative Effects in Mice of Purified Bacterial Cell-Wall Components on Granulocyte-Macrophage Progenitor Cells and Their Regulators¹

From the Cancer Research Unit, The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, 3050, Australia

Abstract

The effects were investigated in mice of the injection of chemically pure preparations of three structurally unrelated cell-wall components from Gram-negative bacteria (BCWC), lipid A, outer-membrane lipoprotein, and murein on humoral and cellular parameters of granulocyte-macrophage production. Analysis of granulocyte-macrophage progenitor cells (GM-CFC) from normal C57BL/6 mice by velocity sedimentation showed that these cells sedimented as a relatively uniform population with a peak sedimentation velocity between 4.2 and 4.5 mm/hr. Pretreatment of mice with murein caused no significant alteration of this profile. However, GM-CFC from mice injected with either lipid A or lipoprotein sedimented more rapidly than normal. The whole profile was broadened and more than one peak was observed. Sera from mice injected with any of the three components stimulated the growth of GM-CFC in vitro, and at high serum concentrations, the absolute number of colonies and the proportion of pure granulocytic, pure macrophage, and mixed colonies were very similar. However, serial dilution of the sera revealed a significant qualitative difference between post-lipid A serum (PLAS) and post-lipoprotein serum (PLPS) on the one hand and post-murein serum (PMS) on the other hand. Thus, with serial dilution the number of colonies induced decreased more rapidly in the case of PMS than in the case of PLAS or PLPS. At dilutions insufficient to induce any colony growth by themselves both PLAS and PLPS potentiated the growth of GM-CFC stimulated by semi-purified mouse lung-conditioned medium (MLCM), whereas PMS, like normal mouse serum (NMS), had no significant effect.

Footnotes

¹ This work was supported by a research fellowship from the Deutsche Forschungsgemeinschaft and by the Anti-Cancer Council of Victoria, the National Health and Medical Research Council, Canberra and by Contract NOI-CB-74147 from the National Cancer Institute, Washington.