To determine the influence of glucagon-like peptides on the secretion of human pulmonary surfactant, we used human type II pneumocytes. In these cells, GLP-1(7-36) amide and exendin-4 stimulated phosphatidylcholine secretion (PC) and cAMP formation in a concentration-dependent manner; these effects were reversed by exendin(9-39). No changes were observed with other related peptides. The mechanism by which GLP-1(7-36) amide exerts its stimulatory effect was investigated with various agents that are well known to be stimulators or inhibitors of PC secretion. Thus, 8-bromo-cAMP increased and both Rp-cAMPS and H-89, the latter an inhibitor of protein kinase A (PKA), reduced pulmonary surfactant secretion in type II pneumocytes. Also, GLP-1(7-36) amide and TPA exerted additive effects in stimulating PC secretion, and Calph C, a potent inhibitor of protein kinase C (PKC), blocked most of the effect of GLP-1(7-36) amide. By contrast, both the calcium ionophore A23187 and GLP-1(7-36) amide had additive effects in increasing PC secretion, and the specific inhibitor of Ca(2+)-calmodulin-dependent protein kinase (Ca-CM-PK), KN-62, inhibited the effect of A23187 but did not alter the stimulatory action of GLP-1(7-36) amide. Our findings suggest that both PKA and PKC are involved in the stimulatory effects of GLP-1(7-36) amide on PC secretion, whereas this peptide has no effect on PC secretion through a Ca-CM-PK mechanism.

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Aging is characterized by the decline and deregulation of several physiological systems, especially the immune system. The involution of the thymus gland has been identified as one of the key events that precedes the age-related decline in immune function. Whereas the decrease in thymocyte numbers and in the thymic output during thymus atrophy has been analyzed by various authors, very little information is available about the age-associated modifications in thymic macrophages and dendritic cells. Here we present evidence that these thymic stromal cell components are only slightly affected by age.

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TNFa seems to play an important role in the pathogenesis of adult respiratory distress syndrome. We studied the effect of TNFa on phospholipid synthesis by isolated type II pneumocytes and attempted to characterize the role of arachidonate metabolites and the influence of pentoxifylline on such an effect.

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Background. Cytokines are produced by tumor cells in vitro, but evidence for in vivo increased production of cytokines in cancer patients is controversial. Conversely, nitric oxide (NO) is implicated increasingly in the mediation of cytokine effects. Lung cancer patients may show an increased local production of cytokines and NO, and chronic paracrine exposure of epithelial lung cells to these medicators may influence the production of surfactant phosphatidylcholine. Methods. The presence of the cytokine tumor necrosis factor (TNFα), interleukin‐1 (IL‐1), and interleukin‐6 (IL‐6), as well as NO, cyclic guanosine 3′5′monophosphate (cGMP) and phosphatidylcholine levels in bronchoalveolar lavage fluid (BLF) of lung cancer patients were investigated. Bronchoalveolar lavage fluid was obtained from 30 male smokers: 22 patients with squamous cell lung cancer and a subjects without cancer. Results. When compared with the control subjects, the cancer patients had elevated BLF levels of TNFα (1.58 ± 0.47 vs. 0.04 ± 0.02 pg/pg protein, P < 0. 0011, IL‐6 (1.39 t 0.29 vs. 0.04 ± 0.02 pg/pg protein, P < 0.001), and NOZ‐NOS‐ (23.3 ± 5.6 vs 1.1 ± 0.6 nmol/mg protein, P < 0.001). However, phosphatidylcholine levels were lower in those with cancer than in the control subjects (3.0 + 1.2 vs. 24.8 ± 6.4 pg protein, P <0.001). Conclusions. The results showed in vivo production of inflammatory cytokines in human lung cancer and increased tumor‐associated NO production, as suggested by increased levels of nitrite/nitrate in the BLF. A decreased phosphatidylcholine content in the BLF also was found in patients with lung cancer.