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The pulmonary collectins, surfactant proteins A and D (SP-A and SP-D) have been implicated in the regulation of the innate immune system within the lung. In particular, SP-D appears to have both pro- and anti-inflammatory signaling functions. At present, the molecular mechanisms involved in switching between these functions remain unclear. SP-D differs in its quaternary structure from SP-A and the other members of the collectin family, such as C1q, in that it forms large multimers held together by the N-terminal domain, rather than aligning the triple helix domains in the traditional “bunch of flowers” arrangement. There are two cysteine residues within the hydrophobic N terminus of SP-D that are critical for multimer assembly and have been proposed to be involved in stabilizing disulfide bonds. Here we show that these cysteines exist within the reduced state in dodecameric SP-D and form a specific target for S-nitrosylation both in vitro and by endogenous, pulmonary derived nitric oxide (NO) within a rodent acute lung injury model. S-nitrosylation is becoming increasingly recognized as an important post-translational modification with signaling consequences. The formation of S-nitrosothiol (SNO)-SP-D both in vivo and in vitro results in a disruption of SP-D multimers such that trimers become evident. SNO-SP-D but not SP-D, either dodecameric or trimeric, is chemoattractive for macrophages and induces p38 MAPK phosphorylation. The signaling capacity of SNO-SP-D appears to be mediated by binding to calreticulin/CD91. We propose that NO controls the dichotomous nature of this pulmonary collectin and that posttranslational modification by S-nitrosylation causes quaternary structural alterations in SP-D, causing it to switch its inflammatory signaling role. This represents new insight into both the regulation of protein function by S-nitrosylation and NO's role in innate immunity.

An HPLC procedure utilizing reversed-phase chromatography coupled with a coulometric array detection system was developed for the characterization of overall antioxidant status in fruits and vegetables. The method was reliable and sensitive (20 pg to 1 ng detection limit) and can also be used to identify and simultaneously quantify multi-antioxidants including vitamin C, glutathione, phenolic acids, and flavonoids in fruits and vegetables. Each fruit and vegetable aqueous extract showed an unique distribution of chromatographic peaks that could serve as a “fingerprint” for the fruit or vegetable. A significant positive linear correlation was demonstrated in fruit and vegetable aqueous extracts between the total antioxidant activities determined by using oxygen radical absorbance capacity (ORACROO • ) assay and the electrochemical data generated from the coulometric array detectors. From these data, the ORACROO • assay appears to be a valid and useful procedure for measuring total antioxidant activity in extracts of fruits and vegetables. Keywords: Fruit; vegetable; antioxidant; phenolic acid; flavonoid; anthocyanin

Propolis contains a variety of bioactive components and possesses many biological properties. This study was designed to evaluate potential effects of Brazilian green propolis on glucose metabolism and antioxidant function in patients with type 2 diabetes mellitus (T2DM). In the 18-week randomized controlled study, enrolled patients with T2DM were randomly assigned to Brazilian green propolis group (900 mg/day) (n = 32) and control group (n = 33). At the end of the study, no significant difference was found in serum glucose, glycosylated hemoglobin, insulin, aldose reductase or adiponectin between the two groups. However, serum GSH and total polyphenols were significantly increased, and serum carbonyls and lactate dehydrogenase activity were significantly reduced in the Brazilian green propolis group. Serum TNF-α was significantly decreased, whereas serum IL-1β and IL-6 were significantly increased in the Brazilian green propolis group. It is concluded that Brazilian green propolis is effective in improving antioxidant function in T2DM patients.

Opiate abuse has been postulated to be a cofactor in the immunopathogenesis of acquired immunodeficiency syndrome (AIDS). This study evaluated whether methadone, a drug widely prescribed for the treatment of drug abusers with opioid dependence, affects human immunodeficiency virus (HIV) infection of human immune cells. When added to human fetal microglia and blood monocyte-derived macrophage cultures, methadone significantly enhanced HIV infection of these cells. This enhancement was associated with the up-regulation of expression of CCR5, a primary coreceptor for macrophage-tropic HIV entry into macrophages. Most importantly, the addition of methadone to the cultures of latently infected peripheral blood mononuclear cells from HIV-infected patients enhanced viral activation and replication. Although the in vivo relevance of these findings remains to be determined, the data underscore the necessity of further studies to define the role of opioids, including methadone, in the immunopathogenesis of HIV infection and AIDS.

Rationale: The pulmonary phenotype of Hermansky-Pudlak syndrome (HPS) in adults includes foamy alveolar type 2 cells, inflammation, and lung remodeling, but there is no information about ontogeny or early disease mediators. Objectives: To establish the ontogeny of HPS lung disease in an animal model, examine disease mediators, and relate them to patients with HPS1. Methods: Mice with mutations in both HPS1/pale ear and HPS2/ AP3B1/pearl (EPPE mice) were studied longitudinally. Total lung homogenate, lung tissue sections, and bronchoalveolar lavage (BAL) were examined for phospholipid, collagen, histology, cell counts, chemokines, surfactant protein D (SP-D), and S-nitrosylated SP-D. Isolated alveolar epithelial cells were examined for expression of inflammatory mediators, and chemotaxis assays were used to assess their importance. Pulmonary function test results and BAL from patients with HPS1 and normal volunteers were examined for clinical correlation. Measurements and Main Results: EPPE mice develop increased total lung phospholipid, followed by a macrophage-predominant pulmonary inflammation, and lung remodeling including fibrosis.

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