Loss of lymphocyte modulatory control by surfactant lipid extracts from acute hypersensitivity pneumonitis: comparison with sarcoidosis and idiopathic pulmonary fibrosis.

Surfactant components are recognized to exert a regulatory control on lymphocytes in physiological conditions, as testified by in vitro studies. However, what happens following lung injury has not been established. As surfactant composition is altered in interstitial lung diseases, this work was carried out to compare the modulatory impact of normal human alveolar fluids on lymphocyte proliferation, with that from inflammatory lung diseases which are characterized by distinct patterns of immunologically-mediated alterations (i.e. sarcoidosis, acute hypersensitivity pneumonitis, idiopathic pulmonary fibrosis). Thymidine incorporation of allogeneic normal human blood lymphocytes was studied in the presence of total alveolar fluids or lipid extracts from 37 subjects, and phytohaemagglutinin (PHA) as T-cell mitogen. The results show that: 1) total alveolar fluids and lipid extracts from normal subjects share a concentration-dependent suppressive activity on T-cell proliferation; 2) total alveolar fluids from diseased patients have lost this property, either by a lack of suppressive activity (i.e. idiopathic pulmonary fibrosis) or even by enhanced activity (i.e. sarcoidosis and hypersensitivity pneumonitis); 3) lipid extracts from diseased patients still retain the suppressive activity of normal subjects, except for hypersensitivity; and 4) an imbalance in surfactant phospholipids with an increase in the inducers to suppressors ratio is more likely to explain this alteration in hypersensitivity pnuemonitis than changes in total lipid content. In conclusion, alveolar lipid extracts from acute hypersensitivity pnuemonitis have lost the modulatory control normally exerted by surfactant lipids on lymphocyte proliferation in vitro. This alteration may contribute to the invasion of the lung by lymphocytes in acute hypersensitivity pnuemonitis in vivo.

Interleukin-6, interferon-gamma, and phospholipid levels in the alveolar lining fluid of human lungs. Profiles in coal worker's pneumoconiosis and idiopathic pulmonary fibrosis.

Cytokines are widely involved in physiologic as well as immunoinflammatory and fibrosing processes of the lung. The aim of this work was to study, by bronchoalveolar lavage, two groups of human interstitial lung diseases (ILD) with fibrosing propensity (ie, idiopathic pulmonary fibrosis [IPF], n = 10; and coal worker's pneumoconiosis [CWP], n = 15). Patients were compared with nonsmoker control subjects (n = 20). Cellularity, proteins, and phospholipids were determined in the alveolar fluids. In addition, two cytokines (interleukin-6 [IL-6] and interferon-gamma [IFN-gamma]), which are presumed to possess respective antifibrotic and profibrotic activities, were measured in the respiratory tract. Compared with control subjects, IPF and simple CWP showed alveolar hypercellularity (p < 0.05) and relative lymphocytosis (p < 0.05). Both exhibited increased alveolar permeability (ie, increased albumin/urea ratio, p < 0.05), with enhanced IL-6 and decreased IFN-gamma in the alveolar spaces (p < 0.05). On the other hand, IPF displayed an associated polymorphonuclear alveolitis, enhanced alveolar epithelial lining fluid (AELF) volume and low surfactant phospholipid levels (p < 0.05 vs control), whereas simple CWP shared an exclusive lymphocytosis, normal AELF volume, and a surfactant lipid overflow (p < 0.05 vs control). Relationships among all of these parameters were found only between alveolar cellularity, neutrophils and IL-6 levels in the AELF of IPF (respectively, r = 0.85, p = 0.0009, and r = 0.89, p = 0.0006). In summary, common alterations of cellular and cytokine turnover were observed in IPF and simple CWP and may reflect activity of the antifibrotic fight in these diseased lungs. Surfactant phospholipid levels are likely to represent a specific disturbance among IPF and CWP, but no clear relationship with respect to the other parameters could be established for explaining the difference in time course outcome.

Early effects of short-time cigarette smoking on the human lung: a study of bronchoalveolar lavage fluids.

We investigated the early effects of cigarette smoking in healthy subjects by means of lung lavage, looking at markers of alveolar permeability, the alveolar cell profile, the immunophenotyping of macrophages and lymphocytes, and the level and profile of surfactant phospholipids. Bronchoalveolar lavages (BAL) were performed in 33 healthy subjects [20 nonsmokers (nS), 13 moderate and short-time smokers (S)]. In the acellular supernatants we measured the markers of alveolar permeability (i.e., total proteins, albumin, albumin/urea), the alveolar epithelial lining fluid (AELF), the surfactant amounts and profile, and explored the blood lymphocytes by in vitro exposure. The cell pellet established the alveolar formula and a membrane mapping of macrophages (LFA-1 and HLA-DRII expression) and lymphocytes (CD4, CD8, LFA-1, HLA-DRII expression). We found no significant increase of alveolar permeability in our smokers, but an increased alveolar cellularity (more than 3-fold vs nS, P < 0.05) evenly distributed between sub-populations except for an enhanced number of eosinophils in smokers (P < 0.05 vs nS). Smokers' alveolar macrophages had an overloaded cytoplasm, a decreased percentage of antigen-handling cell expression (HLA DRII: P < 0.05 vs nS) and a low percentage of cell to cell adhesion molecule expression (LFA-1: P < 0.05 vs nS). Smoking history and LFA-1 expression on alveolar macrophages were interrelated. Smokers' alveolar lymphocyte subsets were more often T suppressor cells (CD8+) and had an increased percentage of antigen-presenting cell expression (HLA DRII: P < 0.05 vs nS). Smokers' BAL fluid did not show the inhibitory control of phytohemagglutinin-induced lymphocyte proliferation present in nonsmokers' fluids. Surfactant phospholipid amounts were similar, but phosphatidylethanolamine was raised and the ratio of phosphatidylcholine to sphingomyelin decreased in smokers (P < 0.05 vs nS). We observed specific cellular and biochemical alterations in the lung lavage of short-time smokers. Alveolar macrophage and lymphocyte expression of LFA-1 and HLA-DR II molecules was altered. Smokers' alveolar fluids lost the physiologic regulatory control of T mitogen-induced lymphocyte proliferation. Membrane phospholipids released by cellular damage increased early in tobacco-exposed lung fluids. This profile of alterations may be an early and sensitive marker of smoking-induced lung damage.