Erythromycin and other antibiotics have been used empirically in the treatment of patients with chronic obstructive pulmonary disease (COPD). We studied whether this empirical role of antibiotics might not be related to a possible direct effect on respiratory glycoconjugate (RGC) secretion. The effect of erythromycin on RGC secretion and hypersecretion was studied in an in vitro preparation of human airways that were secreting [3H]glucosamine respiratory glycoconjugate (RGC), and on a human endometrial adenocarcinoma cell line secreting a glycoconjugate (tumor glycoconjugate = TGC) chemically similar to the RGC secreted by the airways. Erythromycin at 10(-5) M reduced RGC secretion by 35 +/- 4% (n = 9, p less than 0.001) in both human airways and the adenocarcinoma cells, and was increasingly active in the pharmacologic range of 10(-7) to 10(-4) M. The inhibitory effect of erythromycin was maximal within 16 h and was still evident 34 h after incubation. Erythromycin was noted to reduce both spontaneous (baseline) and stimulated RGC secretion (by histamine and methacholine) from airways in culture. The blocking effect appeared to be more selective for histamine than methacholine. These effects were not associated with any toxicity to the tissues and were not associated with the inhibition of protein synthesis. Dexamethasone also inhibited RGC release in both assay systems and exhibited dose-related effects in the physiologic ranges (10(-9) to 10(-5) M). When administered together, erythromycin and dexamethasone had an additive inhibitory effect on RGC secretion (68.0 +/- 3.0%, n = 7, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of major histocompatibility complex (MHC) class II antigens is a requirement for accessory cell function in antigen presentation. Recent reports have demonstrated the presence of class II antigens on human bronchial epithelial cells. In the present study, immunohistochemical staining revealed HLA-DR on human airway epithelial cells obtained from two different mucosal sites (lobar bronchus and nasal turbinates). To determine whether airway epithelial cells bear functional class II molecules that allow for their cognate interaction with T lymphocytes, cells isolated from these sites were used in mixed lymphocyte cultures (MLR), as an in vitro model of accessory cell function. Freshly isolated cells (11 bronchi/3 turbinates) stimulated allogeneic T lymphocytes (stimulation index [S.I.] = 9.3 [mean]; P less than 0.001 compared to T cells alone). In order to assess the potential role of contaminating conventional accessory cells, bronchial epithelial cell isolates were first preincubated in a serum-free, growth factor-supplemented medium that functionally eliminates potential non-epithelial stimulators prior to MLR culture. Conventional accessory cell-depleted epithelial cells were still capable of stimulating allogenic T lymphocytes in 18 of 23 MLR cultures (S.I. = 5.5 [mean]; P less than 0.0005 compared to T cells alone). The addition of an anti-class II monoclonal antibody (VG2.2) at the onset of culture completely inhibited the MLR response (n = 10). No shift in the CD4+/CD8+ ratio was detected between lymphocytes harvested from airway epithelial cell MLR (1.42 +/- 1.29) and the ratio from T lymphocytes cultured alone (1.3 +/- 0.75), suggesting that both CD4+ and CD8+ T lymphocytes were proliferating in response to stimulation from alloepitopes recognized on airway epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

A B S T R A C T (eicosa-5,8, 11,14-tetraynoic acid; vitamin E; nordihydroguaiaretic acid; and a-naphthol) inhibit mucous release. Three additional lines of evidence directly indicate that miionohydroxyeicosatetraenoic acid (HETE) causes increased mucous release: (a) the addition of a mixture of synthetic HETE (24-600 nM) increases mucous release; (b) pure 12-HETE (1-100 nM) also increases mucous release; (c) mucous release is increased synergistically by the combination of HETE and NSIAD.

No abstract