Abstract
Monolayers of murine fibrosarcoma cells that had been treated either with histone-opsonized streptococci, histone-opsonizedCandida globerata, or lipoteichoic acid-anti-lipoteichoic acid complexes underwent disruption when incubated with human polymorphonuclear leukocytes (PMNs). Although the architecture of the monolayers was destroyed, the target cells were not killed. The destruction of the monolayers was totally inhibited by proteinase inhibitors, suggesting that the detachment of the cells from the monolayers and aggregation in suspension were induced by proteinases released from the activated PMNs. Monolayers of normal endothelial cells and fibroblasts were much more resistant to the monolayer-disrupting effects of the PMNs than were the fibrosarcoma cells. Although the fibrosarcoma cells were resistant to killing by PMNs, killing was promoted by the addition of sodium azide (a catalase inhibitor). This suggests that the failure of the PMNs to kill the target cells was due to catalase inhibition of the hydrogen peroxide produced by the activated PMNs. Target cell killing that occurred in the presence of sodium azide was reduced by the addition of a “cocktail” containing methionine, histidine, and deferoxamine mesylate, suggesting that hydroxyl radicals but not myeloperoxidase-catalayzed products were responsible for cell killing. The relative ease with which the murine fibrosarcoma cells can be released from their substratum by the action of PMNs, coupled with their insensitivity to PMN-mediated killing, may explain why the presence of large numbers of PMNs at the site of tumors produced in experimental animals by the fibrosarcoma cells is associated with an unfavorable outcome.
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Supported by a research grant from Dr. S.M. Robbins, Cleveland, Ohio; by research grant IM-432 from the American Cancer Society and by grants HL-28872, HL-37963 and GM-29501 from the National Institutes of Health, Bethesda, MD. Isaac Ginsburg was a visiting professor at the Department of Pathology in 1987–1988.
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Ginsburg, I., Gibbs, D.F. & Varani, J. Interaction of mammalian cells with polymorphonuclear leukocytes: Relative sensitivity to monolayer disruption and killing. Inflammation 13, 529–542 (1989). https://doi.org/10.1007/BF00916759
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DOI: https://doi.org/10.1007/BF00916759