Diesel particles increase phosphatidylcholine release through a NO pathway in alveolar type II cells

Abstract

(DEPs) have been shown in vivo as well as in vitro to affect the respiratory function and in particular the immune response to infection and allergens. In the current study, we investigated the effect of DEPs on the production of phosphatidylcholine (PC), a major constituent of surfactant, by rat alveolar type II (ATII) primary cells in vitro. Our results demonstrate that incubation of ATII cells with DEPs lead to a time-and dose-dependent increase in labeled PC release. This effect was mimicked by nitric oxide (NO) donors and cGMP and was abolished by inhibitors of NO synthase (NOS). In addition, a NOS inhibitor inhibits by itself the basal secretion of PC. We next examined the effects of DEPs on NOS gene expression and showed that DEPs increase NO production and upregulate both protein content and mRNA levels of the inducible NOS (NOS II). Together our data demonstrate that DEPs alter the production of surfactant by ATII cells through a NO-dependent signaling pathway. surfactant; nitric oxide MAJOR AIR POLLUTANTS include nitrogen dioxide, ozone sulfur dioxide, and breathable particulate matter of diameter inferior to 10 m (PM10) (12,27). Several studies have particularly implicated diesel exhaust particles (DEPs), a major component of PM10, as contributing to the incidence and severity of respiratory diseases during air pollution episodes. Epidemiological studies have reported that high levels of DEPs are associated with worsening peak flow, inhaler usage, respiratory symptoms, and emergency room visits in asthmatic children and adults (34,38). In a cohort of over half a million adults residing in 151 metropolitan areas in the United States between 1982 and 1989, fine particulate pollution was associated with cardiopulmonary and lung cancer mortality (33). Similarly, a recent work has demonstrated an increased mortality and morbidity rate after DEPs exposure (26).Airway epithelial cells are primary targets for air pollutants. Several studies have investigated the effect of DEPs on nasal, bronchial, and alveolar epithelial cells. In nasal cells, DEPs enhance cytokine expression synergistically with allergens and increase local eosinophil adhesion (15,16,44). In bronchial epithelial cells, DEPs are internalized, inducing airway inflammation (4,8,41) and hyperresponsiveness (43).DEPs also interact with alveolar type II (ATII) cells since their small size (0.1-1 m) allows them to reach the alveolar space (32,46,48). ATII cells regulate the intra-alveolar homeostasis through four main functions. They secrete a large panel of cytokines (5, 13, 31, 39), serve as progenitors to the alveolar type I cells (18), actively transport ions (23), and synthesize and secrete surfactant. We previously demonstrated that one of these functions (i.e., cytokine secretion) was altered by DEPs (24). Synthesis and secretion of surfactant are other very important functions of ATII cells. Surfactant prevents alveolar collapse at end expiration by lowering surface tension at the air/extracellular lining interface in the alveoli and dist...

9,10-Phenanthrenequinone promotes secretion of pulmonary aldo-keto reductases with surfactant

“…Considering that the pulmonary surfactant contains α-tocopherol (Rüstow et al 1993) in addition to the two antioxidant proteins, the enhanced surfactant secretion is feasibly a cytoprotective response of alveolar type II cells to oxygen radical formation on 9,10-PQ exposure. Experiments on rat alveolar type II primary cells have shown that DEP components, particularly polyaromatic hydrocarbons, induce the release of phosphatidylcholine into the alveolar space through a nitric-oxide-dependent signaling pathway (Juvin et al 2002). Therefore, 9,10-PQ might be a major component in DEP involved in the over-secretion of surfactant, although the mechanism underlying the quinone-mediated surfactant secretion and NO production in the type II cells remains unclear.…”

In vivo comparison of epithelial responses for S-8 versus JP-8 jet fuels below permissible exposure limit

“…These data suggest that surfactant synthesis and/or secretory processes were affected by JP-8 exposure, as indicated by an increase in volume density of surfactant-producting lamellar bodies. Consequently, the type II epithelial cells may compromise their normal capabilities to control the volume and composition of the epithelial lining fluid and to maintain the integrity of the alveolar wall (Juvin et al, 2002). However, S-8 exposure significantly decreases the volume density of mitochondria, as indicative of the onset of cell swelling, when compared to JP-8 group,…”

Reactive Species Mediate Inhibition of Alveolar Type II Sodium Transport during Mycoplasma Infection

“…Correlation of in vitro data to the in vivo disease state is often difficult. Primary ATII cells have been shown to up-regulate iNOS and NO production in response to hyperoxia (21), diesel particles (69), and endotoxin (56). The ability of mycoplasmas to significantly increase NO production after 24 h indicates that damage from reactive nitrogen species to ENaC under these conditions remains a possibility.…”