Several functions of alveolar macrophages (AM) are modified by cigarette smoking. AM are the first line of defense in bronchoalveolar spaces and could be depressed in their cytotoxicity to tumor cells in smokers. An assay using A549 cells (human lung adenocarcinoma) as target cells was performed to assess cytostasis mediated by AM and their supernatants (SN) from healthy smokers (n = 8) and nonsmokers (n = 6). Contact-mediated cytostasis was decreased in AM of smokers (n = 8) relative to nonsmokers (n = 6) (22.9 +/- 5.7% versus 42.7 +/- 6.0% [+/- SEM], P < 0.04) and increased after lipopolysaccharide (LPS) stimulation in both groups (34.5 +/- 5.3% versus 46.8 +/- 5.2%, NS). Cytostasis induced by SN from nonstimulated AM was low in both groups and was still lower in smokers after LPS exposure (19.3 +/- 4.5% versus 34.5 +/- 4.8%, P < 0.04). Among cytotoxic factors produced by macrophages, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) may play an important role in cytostasis. Recombinant human (rH) IL-1 beta and rHTNF alpha had a moderate cytostatic activity, which was additive, whereas rHIL-6 had no significant activity on A549 cells. Bioactive IL-1 beta, IL-6, and TNF alpha were therefore measured in macrophage SN. Their levels tended to be lower in smokers than in nonsmokers and were much increased after LPS stimulation. Levels of the three cytokines were also found to correlate with each other; furthermore, a good correlation between cytokine levels in SN and cytostasis was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

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This study reports the establishment of three major subtypes of human mesothelioma cells in tissue culture, i.e. the epithelioid, sarcomatoid and biphasic forms, and compares their phenotypic and biological characteristics. Primary cells isolated from biopsies or pleural exudates were subcultured for over 50 passages. We evaluated immunoreactivity using various mesothelial markers related to histological patterns of these cell lines. For epithelioid cells, calretinin and cytokeratin were found to be useful and easily interpretable markers as for control mesothelial cells. The biphasic form was only partially positive and the sarcomatoid type negative. Vimentin was expressed by all cell lines. BerEP4, a specific marker for adenocarcinoma, was negative. Interestingly, while the macrophage marker CD14 was negative, immunoreactivity for a mature macrophage marker (CD68) was expressed by all cell types, suggesting that this marker might constitute an additional tool useful in the differential diagnosis of mesothelioma. At the ultrastructural level, a cell surface rich in microvilli confirmed their mesothelial origin. PCR analysis revealed that none of the cell lines contained SV40 DNA. Karyotypic analyses showed more complex abnormalities in the epithelioid subtype than in the sarcomatoid form. These cell lines may be useful in the study of cellular, molecular and genetic aspects of the disease.

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