OBJECTIVETo study the variation and clinical significance of serum levels of surfactant proteins A (SP-A) and D (SP-D) among children with different degrees of bronchiolitis.

METHODSSeventy children with bronchiolitis were divided into acute (n=42) and recovery phase groups (n=28). According to the severity of symptoms, the acute phase group was further divided into severe (n=12) and mild subgroups (n=30). Another 26 children who were hospitalized in the same period due to non-infectious diseases and had not undergone surgery were used as the control group. Competitive enzyme-linked immunosorbent assay was performed to measure serum levels of SP-A and SP-D in each group.

RESULTSThe acute phase group had significantly higher serum levels of SP-A and SP-D compared with the recovery phase (P<0.01) and control groups (P<0.01). Compared with the control group, the recovery phase group had elevated levels of SP-A and SP-D (P<0.01). Within the acute phase group, serum levels of SP-A and SP-D in the severe subgroup were significantly higher than in the mild subgroup (P<0.01).

CONCLUSIONSSerum levels of SP-A and SP-D are significantly elevated in children with acute bronchiolitis, and severe cases have higher serum levels of SP-A and SP-D than mild cases. Even after the relief of clinical symptoms, serum levels of SP-A and SP-D remain high. These findings suggest that serum levels of SP-A and SP-D might be useful biomarkers for evaluating the severity of bronchiolitis among children.

Acute Disease ; Biomarkers ; Bronchiolitis ; blood ; Female ; Humans ; Infant ; Male ; Pulmonary Surfactant-Associated Protein A ; blood ; Pulmonary Surfactant-Associated Protein D ; blood ; Severity of Illness Index

BACKGROUND: Platelet-activating factor(PAF) might play an important role in the development of acute respiratory distress syndrome. Since PAF induced lung injury is similar to changes of acute respiratory distress syndrome, and abnormalities in surfactant function have been described in acute respiratory distress syndrome, the authors investigated the effects of PAF on the regulation of surfactant protein A, B and C mRNA accumulation METHOD: The effects of PAF on gene expression of surfactant protein A, B and C in 24 hours after intratracheal injection of PAF in rats. Surfactant protein A, B and C mRNAs were measured by filter hybridization. RESULTS: The accumulation of SP-A mRNA in PAF treated group was significantly decreased by 37.1% and 41.6%, respectively compared to the control group and the group treated with Lyso-PAF(p<0.025, p<0.01). The accumulation of SP-B mRNA in PAF treated group was decreased by 18.7% and 32.2 %, respectively compared to the control group and the group treated with Lyso-PAF but statistically not significant. The accumulation of SP-C mRNA in PAF treated group was significantly decreased by 30.7% and 38.5%, respectively compared to the control group and the group treated with Lyso-PAF(p<0.01, p<0.01). CONCLUSION: These findings represent a marked inhibitory effects of platelet-activating factor on surfactant proteins expression in vivo. This supports, in turn, platelet-activating factor might be related to pathogenesis of acute respiratory distress syndrome.
Animals ; Gene Expression* ; Lung Injury ; Pulmonary Surfactant-Associated Protein A* ; Rats* ; Respiratory Distress Syndrome, Adult ; RNA, Messenger

BACKGROUND AND OBJECTIVES: Surfactant protein-A (SP-A) is a member of the collectin family, and plays an important role in the first-line airway defense. The purpose of study was to examine the expression of SP-A mRNA and protein in human salivary glands, and to investigate its up-regulation during inflammatory conditions of salivary glands. MATERIALS AND METHOD: Reverse transcription-polymerase chain reaction was performed on salivary gland tissues from ten patients with chronic sialadenitis and ten samples of normal salivary gland tissue. The expression levels of SP-A to GAPDH (glyceraldehyde-3-phosphate dehydrogenase) transcripts were semi-quantified by densitometry. We also characterized the cellular localizations of SP-A protein immunohistochemically. RESULTS: SP-A mRNA and protein were detected in normal and chronic sialadenitis glands. The expression levels of SP-A mRNA in salivary glands with chronic sialadenitis was significantly increased as compared with normal salivary glands. Immunohistochemical staining revealed SP-A immunoreactivity in the ductal epithelia of normal salivary glands and chronic sialadenitis, and stronger immunoreactivity was observed in chronic sialadenitis tissues. CONCLUSION: SP-A is present in the human salivary gland epithelium and is up-regulated during chronic sialadenitis. These results suggest that salivary gland SP-A may play an important role in the innate host defense of human salivary glands.
Collectins ; Densitometry ; Epithelium ; Humans ; Pulmonary Surfactant-Associated Protein A ; RNA, Messenger ; Salivary Glands ; Sialadenitis* ; Up-Regulation*

OBJECTIVETo investigate the effects of maternally administered dexamethasone and ambroxol on the mRNA levels of surfactant proteins (SP-A, SP-B and SP-C) expression in fetal rat lungs at gestational age day 19.

METHODSA 19-day fetal rat lung model was employed. In situ hybridization was used to detect the expression of SP-B mRNA in alveolar type II cell, and the levels of SP-A, SP-B and SP-C mRNAs were detected by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).

RESULTS(1) SP-B mRNA was detected in situ in alveolar type II cells in fetal rat lung of day 19 gestational age; (2) In the late developmental period of fetal rat lungs, alveolar type II cells were also found around bronchus; (3) Comparing to beta-actin mRNA, the relative values of SP-A, SP-B and SP-C mRNAs were 0.81 +/- 0.26, 0.97 +/- 0.20 and 0.88 +/- 0.11 in fetal lung in the control group. The relative values of mRNAs of SP-A, SP-B and SP-C to beta-actin were 1.04 +/- 0.16, 1.28 +/- 0.29, 1.09 +/- 0.25 in fetal lungs of the ambroxol injected rats, and were 1.08 +/- 0.25, 1.23 +/- 0.35, 1.21 +/- 0.25 in fetal lungs of the dexamethasone injected rats, respectively. Both ambroxol and dexamethasone-treated rats had significantly higher mRNA expression of surfactant proteins compared to the control saline injected animals (P < 0.05). (4) There were no significant differences between ambroxol and dexamethasone in the effects of increasing expressions of surfactant protein mRNAs (P > 0.05).

CONCLUSIONAntepartum administration of both ambroxol and dexamethasone can significantly increase fetal lung SP-A, SP-B and SP-C mRNAs expression.

Ambroxol ; pharmacology ; Animals ; Dexamethasone ; pharmacology ; Expectorants ; pharmacology ; Female ; Gene Expression Regulation, Developmental ; drug effects ; Glucocorticoids ; pharmacology ; Lung ; drug effects ; embryology ; metabolism ; Pregnancy ; Pulmonary Surfactant-Associated Protein A ; genetics ; Pulmonary Surfactant-Associated Protein B ; genetics ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactant-Associated Proteins ; genetics ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction

BACKGROUND AND OBJECTIVES: Collectins (surfactant protein A and D) are proteins with collagen tails and globular lectin domains that appear to play an important role in the first line of host defense in mammalians. However, it is not known if collectins are also present in human nasal mucosa. The purpose of this study was to investigate the expression of collectin proteins in human nasal mucosa and to compare the expressions of SP-A and D mRNA in the normal nasal mucosa and in chronic inflammatory nasal diseases. MATERIALS AND METHOD: Ten chronic rhinosinusitis patients were recruited and ten normal nasal mucosae were used as normal controls. Reverse transcriptase-polymerase chain reaction was performed to detect SP-A and SP-D mRNA. The level of collectin and GAPDH (glyceraldehyde-3-phosphate dehydrogenase) transcripts were semi-quantified with the desitometry. We have characterized the cellular localization of SP-A and SP-D protein using immunohistochemistry. RESULTS: SP-A2/GAPDH mRNA ratio in chronic rhinitis nasal mucosa is greater compared with that in normal nasal mucosa (p<0.05). SP-A protein was expressed in the nasal epithelium and in the epithelial cells of the submucosal glands. SP-D mRNA and protein were not expressed in the nasal mucosa. CONCLUSION: These data provide the first evidence of the presence of collectins in the human nasal mucosa. These results suggested that up-regulation of collectin in chronic rhinosinusitis may be a protective response for the nasal mucosa.
Collagen ; Collectins* ; Epithelial Cells ; Humans* ; Immunohistochemistry ; Nasal Mucosa* ; Nose Diseases ; Pulmonary Surfactant-Associated Protein A ; Pulmonary Surfactant-Associated Protein D ; Pulmonary Surfactants ; Rhinitis ; RNA, Messenger ; Sinusitis ; Staphylococcal Protein A ; Up-Regulation

OBJECTIVE: Surfactant protein (SP)-A and SP-D are involved in host defense mechanism. The author was prompted to perform a study on morphologic change and SP-A, SP-D level of surfactant after pulmonary injury inflicted by intratracheal bleomycin injection. METHODS: Fifteen white adult rats each weighing 250 g (Sprague-Daw ley) were divided into study (receiving bleomycin, n=9) and control groups (n=6). Study group were given a intratracheal injection of belomycin (5 mg/kg). Two groups were grown for five weeks at twenty five degrees Celsius, after which lung tissue were examined for morphologic change and SP-A and SP-D levels were measured using Western blot assay with densitometer. RESULTS: Before the study, the average weight of the study group was 286.69+/-14.54 g, and control was 286.69+/-14.54 g. Five weeks later, the average weight of the study group was 347.31.31+/-60.53 g and control group 352.71+/-16.84 g. However, no statistical significance was noted. On light microscopy, the control group exhibited normal findings while widening of lung interstitium and fibrotic change coupled with more prominent inflammatory cell infiltration were noted in the study group. The SP-A level were 15.34+/-1.52 ODU/microgram in the study group and 7.70+/-2.81 ODU/microgram in the control. SP-D level were 3.53+/-1.46 ODU/microgram and 7.51+/-2.33 ODU/microgram in the study and control groups respectively, there was a statistical significance (p<0.05). CONCLUSION: The morphologic change after pulmonary fibrosis induced by intratracheal bleomycin injection in white rats can be summarized as chronic inflammatory cell infiltration, fibroblast proliferation, deposition of collagen tissues, and lowering of SP-D level were noted. The increase of SP-A level is subject to further study in the future.
Adult ; Animals ; Bleomycin ; Blotting, Western ; Collagen ; Fibroblasts ; Humans ; Lung ; Lung Injury ; Microscopy ; Pulmonary Fibrosis* ; Pulmonary Surfactant-Associated Protein D ; Rats*

OBJECTIVETo review the pathophysiology, evaluation, management, and outcomes of children with inherited disorders of surfactant metabolism due to mutations in the genes encoding surfactant proteins-B or -C (SFTPB, SFTPC), ATP binding cassette member A3 (ABCA3), and thyroid transcription factor (NKX2.1).

DATA SOURCESReview of the literature, previous work from the author's and collaborators' laboratories, St. Louis Children's Hospital Lung Transplant Database.

STUDY SELECTIONKey articles in the field, author's work.

RESULTSInherited disorders of surfactant metabolism present as acute, severe respiratory dysfunction in the neonatal period (SFTPB, ABCA3, NKX2.1) or as chronic respiratory insufficiency in later infancy and childhood which is of variable onset, severity, and course (SFTPC, ABCA3, NKX2.1). Diagnosis is established with sequencing the relevant genes; lung biopsy with electron microscopy is a useful adjunct. For surfactant protein-B and ABCA3 deficiency presenting with acute neonatal disease, treatment options are limited to lung transplantation or compassionate care. For the more chronic presentations of surfactant protein-C, ABCA3, and NKX2.1 associated disease, the natural history is variable and therefore individualized, supportive care is appropriate,

CONCLUSIONSInherited disorders of surfactant metabolism are rare, but informative diseases that provide unique opportunities for understanding mechanisms of respiratory disease in newborns and children.

ATP-Binding Cassette Transporters ; genetics ; Humans ; Infant, Newborn ; Lung Diseases ; diagnosis ; etiology ; therapy ; Lung Transplantation ; Mutation ; Pulmonary Surfactant-Associated Protein B ; deficiency ; genetics ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactants ; metabolism

Whether surfactant protein B (SP-B)-18A/C and 1580C/T polymorphism were associated with susceptibility to chronic obstructive pulmonary disease (COPD) in Chinese Han population was investigated. After genomic DNA was isolated from blood of COPD smokers and control smokers, the genotypes of SP-B-18A/C and SP-B1580C/T polymorphism loci were determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) respectively. The results showed that there was significant difference in genotypes distribution frequency of SP-B1580C/T polymorphism locus between COPD smokers and control smokers. C-->T mutation rate (including TT homozygote and CT heterozygote) in COPD smokers was higher than in control smokers (57.9% vs 41.7%, chi2 = 4.93, P<0.05), whereas there was no significant difference in genotypes distribution frequency of SP-B1580-18A/C locus between COPD smokers and control smokers. The allele frequency (29.1%) of SP-B1580-18A/C locus is lower than T allele (70.9%) in Chinese Han Population, and the distribution was different from that in Mexican, in which, the A and T allele frequencies were 85% and 15% respectively. It was concluded that SP-B1580 T allele was probably associated with increased susceptibility to COPD in Chinese Han population; The polymorphism of SP-B-18A/C locus maybe varied with race.
Alleles ; China/ethnology ; Genetic Predisposition to Disease/*genetics ; Genotype ; Polymorphism, Genetic/*genetics ; Pulmonary Disease, Chronic Obstructive/*genetics ; Pulmonary Surfactant-Associated Protein B/*genetics ; Pulmonary Surfactant-Associated Protein B/physiology ; Smoking/genetics

OBJECTIVETo observe the levels of pulmonary surfactant proteins A and D (SP-A, SP-D) in bronchoalveolar lavage fluid (BALF) of children with pneumonia, and to explore their relationships with clinical characteristics.

METHODSThirty-five children with pneumonia were enrolled in this study. Differential cell counts were obtained by Countstar counting board. The levels of SP-A and SP-D in BALF were detected using ELISA.

RESULTSIn children with pneumonia, SP-D levels were significantly higher than SP-A levels (P<0.001). SP-D levels were negatively correlated with the neutrophil percentage in BALF (r(s)=-0.5255, P<0.01). SP-D levels in BALF in children with increased blood C-reactive protein levels (>8 mg/L) were significantly lower than in those with a normal level of C-reactive protein (P<0.05). Compared with those in children without wheezing, SP-D levels in children with wheezing were significantly lower (P<0.01). There was no correlation between SP-A levels and clinical characteristics.

CONCLUSIONSSP-D levels in BALF are significantly higher than SP-A levels, and have a certain correlation with clinical characteristics in children with pneumonia. As a protective factor, SP-D plays a more important role than SP-A in regulating the immune and inflammatory responses.

Bronchoalveolar Lavage Fluid ; chemistry ; C-Reactive Protein ; analysis ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Infant ; Male ; Pneumonia ; metabolism ; Pulmonary Surfactant-Associated Protein A ; analysis ; Pulmonary Surfactant-Associated Protein D ; analysis

Surfactant proteins A (SP-A) and D (SP-D), both members of the collectin family, play a well established role in apoptotic cell recognition and clearance. Recent in vitro data show that SP-A and SP-D interact with apoptotic neutrophils in a distinct manner. SP-A and SP-D bind in a Ca(2+)-dependent manner to viable and early apoptotic neutrophils whereas the much greater interaction with late apoptotic neutrophils is Ca(2+)-independent. Cell surface molecules on the apoptotic target cells responsible for these interactions had not been identified and this study was done to find candidate target molecules. Myeloperoxidase (MPO), a specific intracellular defense molecule of neutrophils that becomes exposed on the outside of the cell upon apoptosis, was identified by affinity purification, mass-spectrometry and western blotting as a novel binding molecule for SP-A and SP-D. To confirm its role in recognition, it was shown that purified immobilised MPO binds SP-A and SP-D, and that MPO is surface-exposed on late apoptotic neutrophils. SP-A and SP-D inhibit binding of an anti-MPO monoclonal Ab to late apoptotic cells. Fluorescence microscopy confirmed that anti-MPO mAb and SP-A/SP-D colocalise on late apoptotic neutrophils. Desmoplakin was identified as a further potential ligand for SP-A, and neutrophil defensin as a target for both proteins.
Apoptosis ; Binding, Competitive ; Fluorescent Antibody Technique, Indirect ; Humans ; Neutrophils ; chemistry ; cytology ; metabolism ; Peroxidase ; isolation & purification ; metabolism ; Protein Binding ; Pulmonary Surfactant-Associated Protein A ; isolation & purification ; metabolism ; Pulmonary Surfactant-Associated Protein D ; isolation & purification ; metabolism