Alveolar macrophage biology

Alveolar macrophages play important roles in lung homeostatic and defense mechanisms. These essential physiologic functions, however, may be subverted. What influences the cells one way or the other? Recent evidence is reviewed. Many of the relevant stimulatory and inhibitory factors are produced by alveolar macrophages themselves.     

Immunologic aspects of pneumoconiosis.

This review summarizes recent research bearing on the role played by cells of the immune system in the development of pneumoconiosis. Findings related to the cellular and humoral immune responses to silica and asbestos are highlighted. Experimental results from humans and animal models are integrated into our current understandings of cellular and cytokine-mediated pathways leading to the generation of immune responses that may contribute to fibrogenesis and fibrosis. Potential mechanisms leading to the generation of an immune response by particulates are discussed, together with the indirect effects of particulates on fibroblasts by way of the cytokine network in the lung. Finally, suggestions are given for future research to help further elucidate the relationships between the cellular components of the immune system of the lung and the fibroblast that lead to fibrosis.     

Protection of p53 Wild Type Cells From Taxol by Genistein in the Combined Treatment of Lung Cancer

This study specifies the basic principles to selectively kill p53-deficient cells (H1299, FaDu) by taxol and to protect p53 wild type cells (A549) by the prior administration of structurally related flavonoids (apigenin, genistein, and quercetin). Cytotoxic and cytostatic properties of flavonoids were investigated in vitro by flow cytometry and were compared to known anticancer drugs (cisplatin, doxorubicin, etoposide). It was confirmed that doxorubicin induced growth arrest and protected A549 cells from taxol while simultaneously killing or blocking H1299 and FaDu cancer cells. It was found that doxorubicin could be successfully substituted in this way by the isoflavone genistein used at physiologically relevant concentrations. The other compounds analyzed revealed less selectivity (apigenin, cisplatin) or demonstrated higher toxicity (cisplatin, etoposide, and quercetin). We concluded that genistein-based therapy may have antagonistic effects when combined with mitotic poisons. The proposed therapeutic strategy allows protection of p53 wild type cells from taxol and selectively increases apoptosis in p53-deficient cells. This strategy exploits the naturally occurring compound that can be used without significant toxicity in rather high concentrations as present in common diets.     

Pulmonary toxicity of simulated lunar and Martian dusts in mice: II. Biomarkers of acute responses after intratracheal instillation

Volcanic ashes from Arizona and Hawaii, with chemical and mineral properties similar to those of lunar and Martian soils, respectively, are used by the National Aeronautics and Space Administration (NASA) to simulate lunar and Martian environments for instrument tests. NASA needs toxicity data on these volcanic soils to assess health risks from potential exposures of workers in facilities where these soil simulants are used. In this study we investigated the acute effects of lunar soil simulant (LSS) and Martian soil simulant (MSS), as a complement to a histopathological study assessing their subchronic effects (Lam et al., 2002). Fine dust of LSS, MSS, TiO(2), or quartz suspended in saline was intratracheally instilled into C57Bl/6J mice (4/group) in single doses of 0.1 mg/mouse or 1 mg/mouse. The mice were euthanized 4 or 24 h after the dust treatment, and bronchoalveolar lavage fluid (BALF) was obtained. Statistically significant lower cell viability and higher total protein concentration in the BALF were seen only in mice treated with the high dose of quartz for 4 h and with the high dose of MSS or quartz for 24 h, compared to mice treated only with saline. A significant increase in the percentage of neutrophils was not observed with any dust-treated group at 4 h after the instillation, but was observed after 24 h in all the dust-treated groups. This observation indicates that these dusts were not acutely toxic and the effects were gradual; it took some time for neutrophils to be recruited into and accumulate significantly in the lung. A statistically significant increase in apoptosis of lavaged macrophages from mice 4 h after treatment was found only in the high-dose silica group. The overall results of this study on the acute effects of these dusts in the lung indicate that LSS is slightly more toxic than TiO(2), and that MSS is comparable to quartz. These results were consistent with the subchronic histopathological findings in that the order of severity of lung toxicity was TiO(2) < LSS < MSS < quartz.     

Live birth and infant death record linkage: methodological and policy issues

Using records from Ohio annual vital statistics tapes, we describe a method for linking live birth and infant death certificates and for dealing with late-registered and unregistered births. In our 1985-87 Cleveland and East Cleveland study population, deceased infants with late-registered births were found to be similar to those with timely registered births. Approximately 4.6% of decedents, however, had unregistered births and these tended to be very premature infants from socially disadvantaged backgrounds who died shortly after delivery (including homicides following birth at home). We discuss the policy implications of failing to link infant deaths with unregistered births in studies of birth outcomes.     

Infant mortality and health care in Mexican communities

Data from the 1976-77 Mexican Fertility Survey show a high degree of correlation among community background characteristics, access to medical services and utilization of health care in a sample of 125 localities. All of these factors are related to infant mortality at the bivariate level. Use of prenatal and infant health care, but not proximity to medical personnel and facilities, is found to affect infant survival independently of the community's degree of socio-economic development. The findings point to the need to employ separate measures of medical access and health utilization.     

Lung lining fluid modification of asbestos bioactivity for the alveolar macrophage.

It is likely that chrysotile fibers deposited in the lower respiratory tract become rapidly coated by components of lung lining fluid. Therefore, we have used lung lining fluid and its components as part of an in vitro model to study chrysotile stimulation of superoxide anion production by the alveolar macrophage. In terms of superoxide anion production, lung lining fluid-treated chrysotile was 50% as effective as the untreated fibers. Fractionated lung lining fluid components and pure phospholipids were tested individually for their effects on chrysotile bioactivity. Pretreatment of chrysotile with lung surfactant isolated from a 30,000g pellet of lung lining fluid decreased chrysotile-stimulated superoxide anion production by 90%. The inhibitory activity of lung surfactant was found to reside in a chloroform extract containing hydrophobic proteins and lipids. Total proteolysis of the proteins did not affect the inhibitory activity of the chloroform extract, but treatment with phospholipase C significantly decreased its inhibitory activity. The inhibitory effects of lung surfactant could be simulated with phosphatidylinositol, phosphatidylserine, and phosphatidylglycerol at concentrations equivalent to those found in lung lining fluid. These results strongly suggest that phosphatidylinositol, phosphatidylserine, and phosphatidylglycerol in lung lining fluid can modify chrysotile bioactivity for the alveolar macrophage. Together with previous results indicating that IgG enhances asbestos bioactivity, it would appear that lung lining fluid contains components that can either inhibit or enhance the bioactivity of asbestos and that it is the relative amounts of these components that determines the overall bioactivity of the fiber.