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Abstract Background Investigations on pulmonary macrophages (MΦ) mostly focus on alveolar MΦ (AM) as a well-defined cell population. Characteristics of MΦ in the interstitium, referred to as lung interstitial MΦ (IM), are rather ill-defined. In this study we therefore aimed to elucidate differences between AM and IM obtained from human lung tissue. Methods Human AM and IM were isolated from human non-tumor lung tissue from patients undergoing lung resection. Cell morphology was visualized using either light, electron or confocal microscopy. Phagocytic activity was analyzed by flow cytometry as well as confocal microscopy. Surface marker expression was measured by flow cytometry. Toll-like receptor (TLR) expression patterns as well as cytokine expression upon TLR4 or TLR9 stimulation were assessed by real time RT-PCR and cytokine protein production was measured using a fluorescent bead-based immunoassay. Results IM were found to be smaller and morphologically more heterogeneous than AM, whereas phagocytic activity was similar in both cell types. HLA-DR expression was markedly higher in IM compared to AM. Although analysis of TLR expression profiles revealed no differences between the two cell populations, AM and IM clearly varied in cell reaction upon activation. Both MΦ populations were markedly activated by LPS as well as DNA isolated from attenuated mycobacterial strains (M. bovis H37Ra and BCG). Whereas AM expressed higher amounts of inflammatory cytokines upon activation, IM were more efficient in producing immunoregulatory cytokines, such as IL10, IL1ra, and IL6. Conclusion AM appear to be more effective as a non-specific first line of defence against inhaled pathogens, whereas IM show a more pronounced regulatory function. These dissimilarities should be taken into consideration in future studies on the role of human lung MΦ in the inflammatory response.

Background This study investigates plasma cytokine levels in neonates with the more common left-sided congenital diaphragmatic hernia (CDH) and correlates them with severity of disease indicated by position of the liver. An intrathoracic part of liver is associated with higher need for extracorporeal membrane oxygenation (ECMO) and higher risk for chronic lung disease (CLD). Methods A total of 28 newborns with CDH were subdivided by their liver position in partially intrathoracic (n = 16) and only abdominal (n = 12) position. Only liver-up patients went on ECMO (n = 9) and developed severe/moderate CLD (n = 5). Controls consisted of 19 healthy matched-term neonates. Laboratory samples were extracted from umbilical cord blood and during the neonatal period. Results In umbilical cord blood, CDH patients showed decreased IL-8 values while MIP-1a (macrophage inflammatory protein-1) values were increased. Concerning the severity of CDH, we measured significantly higher levels of TGFb2 in CDH patients with liver-up than in liver-down cases and controls (p < 0.006). During the neonatal period, the concentration of IL-10 and vascular endothelial growth factor (VEGF) showed significant deviations in the liver-up group with need for ECMO (p < 0.009). Conclusion In neonates with CDH, plasma cytokine levels are already altered in utero. TGFb2may work as an early predictor for severity of disease. VEGF and IL-10 could serve as potential biomarkers predicting the course of disease in CDH. [ABSTRACT FROM AUTHOR]

Aim: Transient tachypnea of the newborn (TTN) is a common cause of early respiratory distress in the neonatal period of term infants. Delayed resorption of foetal lung fluid after birth is considered as the main pathophysiological factor. As resorption of foetal lung fluid is a catecholamine dependent process, we aimed at investigating, whether beta1- and beta2-adrenoreceptor (ADRB1, ADRB2) polymorphisms, known to alter catecholamine activity, are operative in TTN., Methods: DNA was collected for genotyping from 73 term newborns suffering from TTN and 55 healthy controls from a Caucasian cohort., Results: TTN infants were more likely to be male (70% vs. 49%; p < 0.05), had a lower mean birthweight (3120 +/- 450 vs. 3396 +/- 504 g; p < 0.001) and gestational age (GA) (38.4 +/- 1.2 vs. 39.4 +/- 1.3 weeks; p < 0.001) and were more often delivered by caesarean section (CS) (71% vs. 26%; p < 0.001). The beta1Ser49Gly polymorphism differed significantly between cases and controls. Multivariate analysis provided beta1Gly49 homozygotes with higher risk for TTN (OR 18.5; 95%CI 1.5-229; p = 0.023) than beta1Ser49 allele carrier. Further analysis showed significant association of T-47C, A46G, C79G and C491T (TACC) haplotype in ADRB2 gene with TTN (p = 0.048)., Conclusion: We conclude that beta1Gly49 homozygosity and TACC haplotype of ADRB2 gene, both loss-of-function genetic variations, may predispose to TTN.