Surfactant phospholipids, surfactant proteins, and inflammatory markers during acute lung injury in children

Todd, David A; Marsh, Michael P.; George, Anne; Henderson, Neil; Barr, Heather A.; Sebastian, Seby; Clark, Graeme T; Koster, Grielof; Clark, Howard; Postle, Anthony D.

doi:10.1097/pcc.0b013e3181ae5a4c

Cited by 52 publications

(52 citation statements)

References 38 publications

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“…A previous study performed in adults with pneumonia, ARDS, or cardiogenic edema showed that in adults with pneumonia the BALF PL and phosphatidylcholine (PC) content were not significantly different compared with controls (2). It is conceivable that the TAs unsaturated-PC derived from inflammatory cells may have contributed to mantain the same amount of TAs PL content in our newborns with pneumonia together with the increase of other surfactant PL classes, either than the sole DSPC (13). Regarding SP-A (%PL) ratio, Dargaville et al (10) expressed SP-A content as weight/volume of ELF, and as opposed to our study, they found that ELF SP-A in infants with respiratory syncytial virus bronchiolitis was, at the peak of the disease, significantly lower compared to controls.…”

Section: Discussionmentioning

confidence: 99%

“…Only two reports have previously described surfactant composition changes during bacterial pneumonia in infants (12,13). Both studies corrected the TA dilution by TA total protein amount; this method is less reliable than the ELF method because of the risk to underestimate the SPs amounts due to the increased alveolar capillary leak during the disease's course (27).…”

Section: Discussionmentioning

confidence: 99%

“…13 C-palmitate enrichment was measured by gas-chromatography-mass-spectrometry (GC-MS, 6890N-5973 inert, Agilent Technologies, Milan, Italy). Results were expressed as mole percent excess referring to a calibration curve (31,38).…”

Section: Methodsmentioning

confidence: 99%

“…Kerr et al (11) found decreased levels of SP-B in the bronchoalveolar lavage fluid (BALF) of children with severe respiratory syncytial virus bronchiolitis, while LeVine et al (12) found concentrations that did not differ from controls in infants with bacterial and viral pneumonia. Moreover, a recent study in children with acute lung injury, showed no change in either BALF SP-B and SP-A concentrations (13).…”

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confidence: 99%

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Surfactant protein B and A concentrations are increased in neonatal pneumonia

et al. 2015

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Background: Term newborns with pneumonia show a reduced pulmonary compliance due to multiple and illdefined factors. Surfactant proteins' (SPs) changes could have a role in the reduced compliance but the matter is still unsettled. The aim of this study was to clarify the meaning of SPs changes during pneumonia in term newborns. Methods: In 28 term ventilated newborns, 13 with pneumonia and 15 with no lung disease, we measured SP-B, SP-A, disaturated-phosphatidylcholine (DSPC), and total phospholipids (PL) concentrations in tracheal aspirates at intubation and close to extubation. We also measured DSPC kinetics using (U-13 C-PA)dipalmitoyl-phosphatidylcholine. results: At baseline, SP-B, expressed as % of PL, was significantly different between the groups, being 3.5-fold higher in pneumonia than controls. Conversely, SP-A did not vary between the groups. At extubation, SP-B and SP-A concentrations had decreased significantly in newborns with pneumonia, while there was no significant change in controls. DSPC t 1/2 was significantly shorter in the pneumonia group (11.8 (5.5-19.8) h vs. 26.6 (19.3-63.6) h, P = 0.011). conclusion: In term newborns with pneumonia, SP-B increases with respect to PL, and DSPC is turned over at a faster rate. Disease's resolution is associated with the restoration of the normal ratio between SP-B and PL.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Surfactant protein B and A concentrations are increased in neonatal pneumonia

et al. 2015

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“…In other cross-sectional cohort study, Todd et al also have shown that SP-D is increased in both BAL and plasma during ALI and that there was significant increase in SP-D breakdown products in the lungs of these patients [78]. The elevated BAL SP-D level was also associated with respiratory dysfunction, inflammation and increase in plasma SP-D and IL-8 levels during ALI [78]. However, an enhanced level of inflammatory markers, together with detection of significant amounts of SP-D breakdown products, during ALI raises the question about which of the pro- or anti-inflammatory forms of SP-D are elevated.…”

Section: 4 Sp-d In Human Studiesmentioning

confidence: 99%

S-nitrosylation of surfactant protein D as a modulator of pulmonary inflammation

Atochina‐Vasserman

2012

Biochimica et Biophysica Acta (BBA) - General Subjects

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Background Surfactant protein D (SP-D) is a member of the family of proteins termed collagen-like lectins “collectins” that play a role in non-antibody-mediated innate immune responses [1]. The primary function of SP-D is the modulation of host defense and inflammation [2]. Scope of Review This review will discuss recent findings on the physiological importance of SP-D S-nitrosylation in biological systems and potential mechanisms that govern SP-D mediated signaling. Major Conclusions SP-D appears to have both pro- and anti-inflammatory signaling functions. SP-D multimerization is a critical feature of its function and plays an important role in efficient innate host defense. Under baseline conditions, SP-D forms a multimer in which the N-termini are hidden in the center and the C-termini are on the surface. This multimeric form of SP-D is limited in its ability to activate inflammation. However, NO can modify key cysteine residues in the hydrophobic tail domain of SP-D resulting in a dissociation of SP-D multimers into trimers, exposing the S-nitrosylated N-termini. The exposed S-nitrosylated tail domain binds to the calreticulin/CD91 receptor complex and initiates a pro-inflammatory response through phosphorylation of p38 and NF-κB activation [3,4]. In addition, the disassembled SP-D loses its ability to block TLR4, which also results in activation of NF-κB. General Significance Recent studies have highlighted the capability of NO to modify SP-D through S-nitrosylation, causing the activation of a pro-inflammatory role for SP-D [3]. This represents a novel mechanism both for the regulation of SP- D function and NO’s role in innate immunity, but also demonstrates the S-nitrosylation can control protein function by regulating quaternary structure.

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Surfactant protein B amount and kinetics in newborn infants: an optimized procedure

et al. 2012

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Surfactant protein B (SP-B) plays a key role in surfactant homeostasis affecting its biophysical properties and physiological function. Recently, a method to measure SP-B amount and kinetics from tracheal aspirates (TAs) became available. The main objective of this study was to improve the critical steps of the procedure to obtain a better SP-B sensitivity. We administered a 24 h continuous infusion of 1 mg/kg/h of 1(13)C-leucine to ten newborn infants. SP-B was isolated from serial TAs and its fractional synthesis rate, secretion time, peak time and half life were derived from (13)C enrichment curves obtained by gas chromatography mass spectrometry. SP-B amount in TAs was also assessed. During the extraction step, acidification and organic solvent ratio optimization doubled the recovery of SP-B from TAs, so did the elongation of the propylation time (from 20 min to 1 h) with enhanced leucine derivatization yield. Measurement of (13)C leucine enrichments, and therefore all SP-B kinetics parameters, were successfully calculated in all TAs samples due to the increase of SP-B yield. SP-B amount was 0.29 (0.16-0.41) % of total phospholipids with a minimum value of 0.08% belonging to one of the respiratory distress syndrome (RDS) patients. In conclusion, this new procedure enables accurate determination of SP-B kinetics even in the presence of low protein amount like in preterm RDS patients.

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Surfactant phospholipids, surfactant proteins, and inflammatory markers during acute lung injury in children

Cited by 52 publications

References 38 publications

Surfactant protein B and A concentrations are increased in neonatal pneumonia

Surfactant protein B and A concentrations are increased in neonatal pneumonia

S-nitrosylation of surfactant protein D as a modulator of pulmonary inflammation

Surfactant protein B amount and kinetics in newborn infants: an optimized procedure

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