Results are presented that demonstrate a heightened responsiveness of human bronchial epithelial cells (HBECs) toward the complement-derived anaphylatoxin C5a when these cells are exposed to cigarette smoke. This C5a response is possible because we show at both the protein and mRNA levels that HBECs constitutively express receptors for C5a (C5aR, CD88). Control (untreated) HBECs responded to C5a (50 nM) by releasing the proinflammatory cytokine IL-8 at low but significant levels. However, exposure of HBECs to 5% cigarette smoke extract (CSE) for at least 15 min resulted in an increase in the ability of an anti-human C5aR Ab to bind to the cell surface. CSE-treated HBECs responded in a dose-dependent fashion to human recombinant C5a and to a conformationally biased decapeptide agonist of C5a (YSFKPMPLaR) by releasing IL-8. The levels of IL-8 released in response to C5a were significantly greater in CSE-treated HBECs than in control HBECs. Moreover, this C5a-mediated release of IL-8 from CSE-treated HBECs was significantly reduced in the presence of the anti-human C5aR Ab. These results indicate that HBECs constitutively express C5aRs and that exposure to environmental irritants such as cigarette smoke modulates the expression and responsiveness of these C5aRs toward the C5a-mediated release of IL-8.
Minimal residual disease in lymphoma patients is a major problem in the clinical management of their cancer. High-dose chemotherapy followed by autologous bone marrow transplantation has been used to treat the disease. However, residual lymphoma may be reintroduced along with the marrow if it is present in the bone marrow harvest. In this report we describe results of experiments testing the efficacy of 5-[125I]-iodo-2'-deoxyuridine (125IdU) for purging murine RAW117 large cell lymphoma cells (Joshi et al., Oncology 44, 180-185, 1987; Cancer Res. 47, 3551-3557, 1987) from bone marrow in a relevant animal model. Donor BALB/c mice were injected with murine RAW117 cells and euthanized on day 13, and their bone marrow that had been contaminated with tumor cells was harvested and treated in vitro with 125IdU or nonradioactive 127IdU (control). Nine of 10 mice receiving 127IdU-treated bone marrow contaminated with tumor cells died at an average of 17 days after injection. In comparison, 9 of 10 mice injected with 125IdU-treated bone marrow contaminated with tumor cells were still alive after 82 days. In addition, the 125IdU treatment did not diminish the formation of hematopoietic progenitor cell colonies in normal mouse and human peripheral blood stem cells.
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