Immunohistochemical distribution of surfactant apoprotein-A in congenital diaphragmatic hernia

Asabe, Koushi; Tsuji, K.; Handa, Noritoshi; Kurosaka, Natsumi; Kajiwara, M.

doi:10.1016/s0022-3468(97)90001-4

Cited by 43 publications

(21 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In congenital diaphragmatic hernia, a decrease in the expression of SP-A has been shown to deter the structural growth of affected lungs and the functional growth of type II alveolar epithelial cells (17). In the present study, we observed reduced SP-A expression in all three infants complicated by congenital diaphragmatic hernia (cases 12, 15, and 16).…”

Section: Discussionsupporting

confidence: 65%

Expression of Intrapulmonary Surfactant Apoprotein-A in Autopsied Lungs: Comparative Study of Cases with or without Pulmonary Hypoplasia

et al. 2000

View full text Add to dashboard Cite

To investigate the functional maturity of the lungs of infants with pulmonary hypoplasia, we measured the expression of surfactant apoprotein-A (SP-A) in the autopsied lungs. Autopsied lungs were taken from 16 infants who died at birth or soon after. A lung-to-body weight ratio of less than 1.2% was defined as pulmonary hypoplasia. Eight infants were classified as belonging to the normal group, and eight as belonging to the pulmonary hypoplasia group. Many of the pulmonary hypoplasia group were complicated not only by pulmonary hypoplasia, but also by amniotic fluid volume abnormalities or an anatomical malformation. We measured the expression of SP-A immunologically using murine anti-human SP-A MAb in the autopsied lung tissue, and subjected the tissue to SP-A staining by the direct staining method. The expression of SP-A was assessed as one of four grades: Ϫ, Ϯ, 1ϩ, 2ϩ. The staining intensity of SP-A was high at 1ϩ or stronger in five infants of the normal group. SP-A expression was significantly reduced, however, in all infants of the pulmonary hypoplasia group except for one infant with normal amniotic fluid volume and relatively mild pulmonary hypoplasia. There was a significant negative correlation between the staining intensity of SP-A and two factors: pulmonary hypoplasia and abnormal amniotic fluid volume (p ϭ 0.039 and p ϭ 0.0063, respectively). In the present study, we demonstrated that SP-A expression was significantly reduced in infants with pulmonary hypoplasia. We speculate that the functional maturity of the lungs of infants with pulmonary hypoplasia is also suppressed. The alveolar lining is composed of type I and type II epithelial cells. Human pulmonary surfactants are lipid-protein complexes (lipoproteins) synthesized in type II cells. These surfactants are secreted into the alveolar space in order to cover the surface of alveoli and thus reduce alveolar surface tension. The functional expression of pulmonary surfactants requires specific proteins (apoproteins). To date, four types of surfactant apoproteins (SP) have been identified: SP-A, SP-B, SP-C, and SP-D. Of these, SP-A is the most prevalent form of SP (1). SP-A is a hydrophilic glycoprotein with a molecular weight of approximately 28 -36 kD, and the level of SP-A in the amniotic fluid, gastric juice, and respiratory aspirate is a useful indicator of the functional maturity of fetal and neonatal lung tissue (2, 3).In the present study, to assess the functional maturity of the lungs of infants with pulmonary hypoplasia, we measured the expression of SP-A immunohistologically using murine antihuman SP-A MAb in the autopsied lungs of infants who died at birth or soon after. METHODS Subjects.Autopsied lungs were taken from 16 infants at some point during a 21-y period between November 1976 and February 1998. Of the 16 infants, 14 came from the Division of Neonatal Intensive Care or the Department of Gynecology and Obstetrics at our hospital. These subjects had died at birth or within 5 d of birth. The remaining two infants came from the Neo...

show abstract

Section: Discussionsupporting

confidence: 65%

Expression of Intrapulmonary Surfactant Apoprotein-A in Autopsied Lungs: Comparative Study of Cases with or without Pulmonary Hypoplasia

et al. 2000

View full text Add to dashboard Cite

show abstract

“…Pulmonary hypoplasia, cardiac and other anomalies, pulmonary immaturity, and surfactant deficiency may contribute to death in these infants. [5][6][7][8] It has been shown in an animal model of CDH that these animals are surfactant deficient and that their respiratory failure can be improved with the administration of exogenous surfactant. 9,10 However, Van Tuyl et al 11 recently showed no deficiency in surfactant mRNA expression in rats with nitrofen-induced CDH.…”

mentioning

confidence: 99%

Surfactant does not improve survival rate in preterm infants with congenital diaphragmatic hernia

2004

Journal of Pediatric Surgery

View full text Add to dashboard Cite

“…Also, normal levels of phospholipids and normal lecithin/ sphingomyelin (L/S) ratios (used as indicator of fetal lung maturity) in amniotic and bronchoalveolar lavage (BAL) fluid have been reported (17,18). Nevertheless, other studies have found decreased amounts of SP-A in human CDH (19,20). It has to be kept in mind that a secondary surfactant deficiency may develop due to the negative effects of artificial ventilation on surfactant function after birth (21).…”

mentioning

confidence: 99%

“…It has to be kept in mind that a secondary surfactant deficiency may develop due to the negative effects of artificial ventilation on surfactant function after birth (21). So far, data from human and different animal CDH models (22) failed to report consistent results concerning the surfactant status in CDH (summarized in Table 1) (17)(18)(19)(20)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39).…”

mentioning

confidence: 99%

Pulmonary Surfactant Protein A, B, and C mRNA and Protein Expression in the Nitrofen-Induced Congenital Diaphragmatic Hernia Rat Model

et al. 2003

View full text Add to dashboard Cite

Neonates with congenital diaphragmatic hernia (CDH) suffer from a diaphragmatic defect, lung hypoplasia, and pulmonary hypertension, with poor lung function forming the major clinical challenge. Despite prenatal diagnosis and advanced postnatal treatment strategies, the mortality rate of CDH is still high. CDH has been subject of extensive research over the past decades, but its etiology remains unknown. A major problem with CDH is the failure to predict the individual response to treatment modalities like high-frequency ventilation, inhaled nitric oxide, and extracorporeal membrane oxygenation. In this study, we tested the possibility that CDH lungs are surfactant protein deficient, which could explain the respiratory failure and difficulties in treating CDH infants. We investigated this hypothesis in the nitrofeninduced CDH rat model and assessed the cellular concentrations of surfactant protein (SP)-A, -B, and -C mRNA with a quantitative radioactive in situ hybridization technique. No differences were observed between control and CDH lungs for SP mRNA expression patterns. The cellular concentration (mean OD) of SP-A and SP-B mRNA was similar at all stages whereas the mean OD of SP-C mRNA and the volume fraction of cells (% Area) expressing SP mRNA was higher in CDH lungs at term. Immunohistochemical analysis revealed no differences between control and CDH lungs for SP protein expression. No differences in the mean OD or % Area for the SP mRNAs were found between the ipsi-and contralateral side of CDH lungs. We conclude that there is no primary deficiency of surfactant proteins in the nitrofen-induced CDH rat model. CDH is an anomaly occurring 1 in 3000 live births (1). It is characterized by a diaphragmatic defect, severe lung hypoplasia, and pulmonary hypertension, and in 40% of the patients other severe birth defects such as cardiac abnormalities are present (2, 3). Despite years of extensive research, the etiology of CDH remains unknown (4). Clinically, pulmonary hypoplasia and pulmonary hypertension form the major problems in CDH (5).Many CDH studies have focused on treatment modalities such as conventional ventilation with gentle handling of the fragile lung, high-frequency ventilation, ECMO, in utero tracheal ligation with or without betamethasone injection, inhaled nitric oxide, and prenatal injections of betamethasone, TSHreleasing hormone, or a combination of both hormones. Although selected centers have reported improved survival (6, 7), the overall mortality rate, however, is still variably high, so that CDH continues to be a serious problem in the neonatal and pediatric surgical intensive care unit, with optimal treatment for CDH still the subject of ongoing debate (5, 8 -10

show abstract

Immunohistochemical distribution of surfactant apoprotein-A in congenital diaphragmatic hernia

Cited by 43 publications

References 20 publications

Expression of Intrapulmonary Surfactant Apoprotein-A in Autopsied Lungs: Comparative Study of Cases with or without Pulmonary Hypoplasia

Expression of Intrapulmonary Surfactant Apoprotein-A in Autopsied Lungs: Comparative Study of Cases with or without Pulmonary Hypoplasia

Surfactant does not improve survival rate in preterm infants with congenital diaphragmatic hernia

Pulmonary Surfactant Protein A, B, and C mRNA and Protein Expression in the Nitrofen-Induced Congenital Diaphragmatic Hernia Rat Model

Contact Info

Product

Resources

About