Direct Activation of Human Peritoneal Mesothelial Cells by Heat-killed Microorganisms

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Abstract
The aim of the study was to determine if human peritoneal mesothelial cells (HPMCs) can be activated directly by bacterial products contained in preparations of heat-killed Escherichia coli and staphylococci. It has been shown recently that cytokine-activated HPMCs produce the inflammatory mediators, interleukin-1, interleukin-6, interleukin-8, and macrophage chemotactic protein-1. Studies concerning the effects of bacterial products on HPMCs are scarce and have not yielded conclusive results. Growth-arrested HPMC monolayers were prepared from cell suspensions obtained by enzymatic disaggregation of small pieces of omentum. They were incubated for 24 hours with heat-killed E. coli (ATCC 25922), heat-killed staphylococci (ATCC 25933), or E. coli lipopolysaccharide, and the release of various cytokines in the culture media was measured by radioimmunoassays or enzyme-linked immunosorbent assays. Results were expressed as mean ± standard error of the mean in picograms per milliliter of supernatant and analyzed with the Wilcoxon test; p values of less than 0.05 were considered significant. Baseline production of interleukin-6, interleukin-8, the chemokine “regulated upon activation, normal T cell expressed and secreted” (RANTES), and macrophage chemotactic protein-1 varied widely from one omental preparation to the other. E. coli increased the release of these mediators: from 1206 ± 316 pg/mL to 8480 ± 2189 pg/mL for interleukin-6, from 285 ± 58 pg/mL to 3164 ± 1053 pg/mL for interleukin-8, from 7 ± 5 pg/mL to 684 ± 264 pg/mL for RANTES, and from 2212 ± 346 pg/mL to 7726 ± 1473 pg/mL for macrophage chemotactic protein-1. Heat-killed staphylococci did not alter significantly the production of RANTES or macrophage chemotactic protein-1 but increased the production of the two other cytokines from 1325 ± 389 pg/mL to 2206 ± 523 pg/mL for interleukin-6 and from 318 ± 70 pg/mL to 819 ± 265 pg/mL for interleukin-8. The authors' results show that HPMCs are able to react to a direct stimulation with heat-killed microbes. They suggest that HPMCs, as well as resident macrophages, participate actively in the initiation and possibly in the modulation of intraperitoneal inflammatory reactions.