Pulmonary surfactant prevents exocytosis that is induced by PolymyxinB.

<p>Fluorescence (lyso tracker green) scattergram of alveolar type II cells after 5 h incubation with mixtures of modified porcine surfactant (SF) and/or Polymyxin B (PxB), 30 min after staining of lamellar bodies, compared to controls (DMEM). Fluorescence in cells exposed to PxB is significantly reduced compared to DMEM, SF or in mixture with SF. Bars show mean ± SD, n = 14–16. *: p<0.01 vs. DMEM, SF and SF plus PxB.</p

Polymyxin B induces exocytosis of alveolar type II cells.

<p>Initial lyso tracker green fluorescence of alveolar type II cells 30 min after staining, comparing cells incubated with Polymyxin B (PxB) to controls (DMEM). The fluorescence in cells exposed to PxB decreases in a time-dependent manner, whereas it remains stable in controls. Bars are mean+SD, n = 14–16. *: p<0.01 vs. DMEM.</p

Viability of alveolar type II cells exposed to surfactant and/or Polymyxin B.

<p>Viability of alveolar type II cells (ATIIC) incubated for 1 h or 5 h with modified porcine surfactant (SF) and/or Polymyxin B (PxB) or DMEM control expressed by resofurin-fluorescence, in which viability is decreased in non-proliferating ATIIC (mean±SD; n = 9). A significant reduction in viability is found in ATIIC incubated with PxB (0.1 mg/ml), but not in cells incubated with SF or a mixture of SF plus PxB. No significant reduction of fluorescence is found in any sample comparing 1 h vs. 3 h.</p>**<p>p<0.01 vs. 1 h (Friedman test of non-Gaussian distributed matched observations.).</p

The association of mannose-binding lectin 2 polymorphisms with outcome in very low birth weight infants

<div><p>Objectives</p><p>Studies on the influence of mannose-binding lectin (MBL) deficiency on infection susceptibility in preterm infants have yielded controversial results. We investigated the association of genotype-based MBL levels with outcome in very-low-birth weight infants (VLBWI).</p><p>Methods</p><p>We genotyped 3 genetic variants of MBL2 (rs1800450, rs1800451, rs5030737) in 6878 VLBWI. MBL plasma levels were categorized as normal (wild type, A/A), low (heterozygotes, A/O) or undetectable (homozygotes, O/O). Primary outcome was the effect of genotype-based MBL2 levels on blood-culture proven and clinical sepsis during primary stay in hospital. We also evaluated burden of infection within 24 months after discharge.</p><p>Results</p><p>We found no association between MBL levels and sepsis risk in the whole cohort. Infants without measurable MBL levels born between 32 0/7 to 36 6/7 weeks of gestation, however, had a higher rate of Gram-negative sepsis than infants with normal or reduced MBL levels. In a follow-up investigation at 24 months (n = 1070 infants), infants without measurable MBL levels suffered more frequently from stomatitis and urinary tract infection.</p><p>Conclusions</p><p>In a large cohort of VLBWI MBL2 deficiency had no major impact on infection risk unless children were born between 32 0/7 and 36 6/7 weeks of gestation.</p></div

Mean outcome distribution according to genotype and phenotype.

*<p>Surgery for necrotizing enterocolitis.</p

Infection risk according to MBL levels in gestational age group 22 0/7–27 6/7 weeks of gestation.

<p>Infection risk according to MBL levels in gestational age group 22 0/7–27 6/7 weeks of gestation.</p

Episodes of herpes stomatitis and bacterial urinary tract infection in the first 24 months of life.

<p>The mean±SD number of episodes of episodes of stomatitis and urinary tract infection (UTI) are based on parents’ responses to the KIGGS questionnaire at 24 months of age. Data are described according to genotype-based MBL levels. Infants without measurable MBL levels had a higher rate of herpes stomatitis as compared to infants with normal MBL levels (p = 0.004) and low MBL levels (p = 0.02) and a higher frequency of bacterial UTI as compared to infants with normal MBL levels (p = 0.03, Mann-Whitney U-test).</p

Episodes of infections in the first 24 months of life according to genotype-based MBL levels.

<p>Episodes of infections in the first 24 months of life according to genotype-based MBL levels.</p

Frequency of MBL2 polymorphisms in the European cohort and number of genotyped infants (PCR + Genome-Wide Association Study).

<p>Frequency of MBL2 polymorphisms in the European cohort and number of genotyped infants (PCR + Genome-Wide Association Study).</p

Clinical characteristics of VLBW cohort according to genotype-based MBL levels.

<p>Clinical characteristics of VLBW cohort according to genotype-based MBL levels.</p