Faculty Bibliography

This is a report of the study on the immunological status of alveolar macrophages (aM phi) in patients with lung cancer (LC, n = 27) and benign pulmonary diseases (BD, n = 26). Patients were undergone bronchoalveolar lavage by fiberoptic bronchoscopy. aM phi in the lavage fluid isolated by adherence on plastic surface were examined in vitro for their cytostatic and cytolytic activities against tumor target cells, secretion of interleukin 1 (IL-1) and tumor necrosis factor (TNF), intracellular IL-1 activity and mRNA expression of IL-1 beta and TNF-alpha. aM phi, both non-activated and activated, were shown to be highly cytostatic against P815 cells by 3H-TdR post-labelling assay. There was no statistical difference between the LC and BD group. As shown by isotope release assay, regardless of being activated or not, aM phi were not cytolytic against P815 and NS-1 cells in both groups of patients. TNF activity could be demonstrated in the culture supernatants of aM stimulated with LPS. Statistically, the TNF activity was not different in the two groups of patients. Spontaneous release of TNF activity was occasionally detected in unstimulated aM phi. While both intracellular and extracellular IL-1 activity of unstimulated aM phi was demonstrated in the two patient groups, the former activity was 1 to 5 times as high as the latter. When stimulated with LPS, there was some increase in extracellular but not intracellular IL-1 activity. mRNA expression of IL-1 beta and TNF-alpha by dot blot hybridization was demonstrable in aM phi from both patient groups irrespective of activation. These results indicate that the immune status of aM phi in lung cancer patients examined does not differ from that in patients with benign pulmonary diseases.

In this paper, the immunoregulatory effects of calcium ionophore A23187 on the accessory function of mouse spleen dendritic cells (DC) in primary mixed lymphocyte reaction (1.MLR) and oxidative mitogenesis are reported. A23187 had a direct enhancing effect on DC. When pretreated with 0.5-1 mumol/L A23187 for 6-8 h, the accessory activity of DC was twice as high as that of the control. This is circumstantial evidence indicating an up-regulation of activity mediated by an increase in intracellular Ca2+ levels and PKC activation.

Dendritic cells (DC) comprise a small subpopulation of lymphoid cells, with distinct morphologic features, surface phenotypes and a potent accessory function in T cell-dependent immune responses. In the present study, we investigated the in vitro effects of a tumor promoter, phorbol myristate acetate (PMA), and calcium ionophore A23187 on the accessory cell function of mouse spleen DCs in the primary mixed lymphocyte reaction (1 degree MLR) and oxidative mitogenesis (OM). A multi-step purification procedure was used to procure a highly enriched DC population from mouse spleen. The accessory cell activity of the DCs so obtained was much stronger than that of M phi s in both MLR and OM. The effects of PMA, a protein kinase C (PKC) activator, on DC were dose-dependent. If pretreated with 50 ng/ml of PMA for 3 h, DC activity was enhanced by about two-fold; whereas 200 ng/ml decreased DC activity with an inhibition rate of about 50%. However, in the latter situation, a moderate increase in DC activity was seen in the early phase of the response. When pretreated with 0.5-1.0 mumol/L A23187 for 6-8 h, the accessory cell activity of DCs was twice as potent as that of the control, and the enhancing effect was sustained in both MLR and OM. Our results indicate that the function of DCs, a cell type with constitutively high accessory cell activity, can be further promoted by A23187 or a low dose of PMA. This is also circumstantial evidence of an up-regulation of DC activity via PKC activation and/or an increase in cytoplasmic calcium.(ABSTRACT TRUNCATED AT 250 WORDS)