Pulmonary surfactant is a lipoprotein substance that lines the lungs and helps reduce surface tension. Surfactant associated protein-A (SP-A) is the most abundant non-serum protein in pulmonary surfactant. This complex glycoprotein aids in the synthesis, secretion and recycling of surfactant phospholipids, and facilitates the reduction of surface tension by surfactant phospholipids. Recent evidence has highlighted the role of SP-A in the innate immune system present in the lung. SP-A may play a major role in defense against pathogens by interacting with both infectious agents and the immune system. Factors that affect fetal lung maturation, e.g., gestational age and hormones, regulate SP-A gene expression. Mediators of immune function also regulate SP-A levels. A number of lung disorders, including infectious diseases and respiratory distress syndrome are associated with abnormal alveolar SP-A levels. SP-A can no longer be called a lung-specific protein, since it has recently been detected in other tissues. In most species, SP-A is encoded by a single gene, however in humans it is encoded by two, very similar genes. Models for the structure of the human SP-A protein molecule have been proposed, suggesting that the mature alveolar SP-A molecule is composed of both gene products. The study of SP-A may provide information helpful in understanding disease processes and formulating new treatment modalities.

Gene Expression↗

PubMedDate not supplied

Surfactant protein-A: new insights into an old protein--II.

Pulmonary surfactant is a lipoprotein substance that lines the lungs and helps reduce surface tension. Surfactant associated protein-A (SP-A) is the most abundant non-serum protein in pulmonary surfactant. This complex glycoprotein aids in the synthesis, secretion and recycling of surfactant phospholipids, and facilitates the reduction of surface tension by surfactant phospholipids. Recent evidence has highlighted the role of SP-A in the innate immune system present in the lung. SP-A may play a major role in defense against pathogens by interacting with both infectious agents and the immune system. Factors that affect fetal lung maturation, e.g. gestational age and hormones regulate SP-A gene expression. Mediators of immune function also regulate SP-A levels. A number of lung disorders, including infectious diseases and respiratory distress syndrome are associated with abnormal alveolar SP-A levels. SP-A can no longer be called a lung-specific protein, since it has recently been detected in other tissues. In most species, SP-A is encoded by a single gene, however in humans it is encoded by two, very similar genes. Models for the structure of the human SP-A protein molecule have been proposed, suggesting that the mature alveolar SP-A molecule is composed of both gene products. The study of SP-A may provide information helpful in understanding disease processes and formulating new treatment modalities.

Gene Expression↗

PubMedDate not supplied

Cochlear summating potential to broadband clicks detected from the human external auditory meatus. A study of subjects with normal hearing for age.

The cochlear summating potential (SP) preceding the auditory nerve compound action potential (AP) was elicited by broadband alternating condensation and rarefaction clicks and recorded by noninvasive electrodes from the external auditory meatus (EAM) of 60 volunteers of both sexes, 12 to 67 years old, who had normal hearing for age. Quantitative data were obtained on: the number of ears displaying measurable SPs; the SP detection level; the SP onset, peak and rise times; the duration of the SP-AP complex; the SP amplitude; and the SP/AP amplitude ratio. Previously unknown relationships were unveiled between the amplitude, but not the temporal, measures of the SP and laterality, sex, age, and audiometrically determined hearing thresholds to 4 to 8 kHz tones. The highest correlations were obtained with these last thresholds, which suggested that receptors in the basal turn of the cochlea played a dominant role in the generation of the EAM-detected SP. To improve on existing techniques for determining abnormal SP elevation, a multiple regression method was devised that utilized sex, age, 4 to 8 kHz hearing thresholds, and AP voltage to establish upper normal limits of SP amplitude for individual subjects and ears.

Acoustic Stimulation↗

PubMedDate not supplied

Electronystagmographic and audiologic findings in patients with Meniere's disease.

Electronystagmographic (ENG) and audiologic findings were reviewed for 206 patients treated for Meniere's disease (MD) at the University of Washington Hospital over a 10-year period (1971-80). The most frequently seen ENG findings were unilateral caloric weakness (UW) in 49%, directional preponderance (DP) in 36%, and spontaneous and/or positional nystagmus (SN, PN) in 32%. ENG was normal in 25%. Bilateral caloric weakness (BW) occurred in 36% of patients with bilateral hearing loss. UW was reliably correlated with the side of audiometric involvement; after exclusion of bilateral cases, only 3% of patients showed UW contralateral to the ear with hearing los. Neither DP nor direction of SN or PN correlated at all with side of hearing loss. There was no significant correlation of severity of hearing loss (by pure-tone thresholds or speech discrimination score) with ENG abnormality (UW or DP). Glycerol-positive patients had significantly poorer hearing than glycerol-negative patients, but ENG findings were similar in the two groups.

Audiometry↗

PubMedDate not supplied

Vitamin E alters alveolar type II cell phospholipid synthesis in oxygen and air.

Newborn rats were injected with vitamin E or placebo daily until 6 days after birth. The effect of vitamin E pretreatment on in vitro surfactant phospholipid synthesis was examined in isolated type II cells exposed to oxygen or air form 24 h in vitro. Type II cells were also isolated from untreated 6-day-old rats and cultured for 24 h in oxygen or air with control medium or vitamin E supplemented medium. These cells were used to examine the effect of vitamin E exposure in vitro on type II cell phospholipid synthesis and ultrastructure. Phosphatidylcholine (PC) synthesis was reduced in cells cultured in oxygen as compared with air. This decrease was not prevented by in vivo pretreatment or in vitro supplementation with vitamin E. Vitamin E pretreatment increased the ratio of disaturated PC to total PC and increased phosphatidylglycerol synthesis. The volume density of lamellar bodies in type II cells was increased in cells maintained in oxygen. Vitamin E did not affect the volume density of lamellar bodies. We conclude that in vitro hyperoxia inhibits alveolar type II cell phosphatidylcholine synthesis without decreasing lamellar body volume density and that supplemental vitamin E does not prevent hyperoxia-induced decrease in phosphatidylcholine synthesis.

Air↗

PubMedDate not supplied

Developmental regulation of surfactant-associated proteins in rabbit fetal lung in vivo.

The developmental regulation of the rabbit surfactant-associated proteins, SP-A, SP-B, and SP-C, was investigated using Northern blot analysis. These proteins comprise approximately 10% by weight of pulmonary surfactant, a lipoprotein secreted by type II cells that reduces surface tension at the air-alveolar interface. SP-A mRNA and SP-B mRNA were first detected in rabbit fetal lung at day 24 of gestation (term = 31 days), i.e., approximately two days prior to the appearance of lamellar bodies within differentiated alveolar type II cells. The relative abundance of SP-B mRNA detected on day 24 of gestation was greater than that of SP-A mRNA. Fetal lung SP-A mRNA and SP-B mRNA levels increased rapidly during the remainder of gestation, reaching a maximum at day 31 of gestation. The relative concentrations of SP-A mRNA and SP-B mRNA were decreased in day 2 neonatal and adult lung tissues when compared to the levels present in fetal lung tissue late in gestation. A 0.5-kb rabbit SP-C cDNA was generated using the reverse transcriptase-polymerase chain reaction and was found to have high sequence homology to the human and rat SP-C cDNA nucleotide sequences. The predicted amino acid sequence for the rabbit SP-C cDNA revealed strong conservation of a hydrophobic region close to the amino terminus of the SP-C protein. Fetal lung SP-C mRNA was detected at day 19 of gestation, the earliest time point examined in this study. SP-C mRNA levels gradually increased in fetal lung tissue until day 28 of gestation and then remained level throughout the remainder of gestation and in the day 2 neonatal and adult rabbit lung tissue. These results suggest that the developmental pattern of induction of mRNA for the surfactant-associated proteins, SP-A, SP-B, and SP-C, differ from each other and are different in several respects from the developmental patterns observed in fetal lung tissue of the rat and human species.

Amino Acid Sequence↗

PubMedDate not supplied

Localization of epidermal growth factor receptor in alveolar epithelium during human fetal lung development in vitro.

Epidermal growth factor (EGF) enhances alveolar type II cell differentiation. In human fetal lung explants, EGF stimulates surfactant protein A (SP-A) synthesis. This effect may occur through a direct interaction of the ligand on EGF receptors located within distal pulmonary epithelium during alveolar type II cell differentiation. To determine if EGF receptor is present in alveolar epithelium, immunostaining for EGF receptor and in situ hybridization for EGF receptor mRNA were performed in human fetal lung explants undergoing alveolar type II cell differentiation in vitro. After 4 days in culture, EGF receptor immunostaining was present in alveolar epithelium from human fetal lung explants compared to minimal immunostaining in undifferentiated human fetal lung epithelium prior to culture. In situ hybridization revealed increased EGF receptor mRNA in differentiated type II cells from cultured explants, with minimal EGF receptor mRNA detected in undifferentiated epithelium from tissue prior to culture. Immunogold staining revealed EGF receptors on the cytoplasmic membranes of epithelial cells lining the prealveolar ducts in human fetal lung explants after 2 days in culture. Alveolar type II cell differentiation in vitro was confirmed ultrastructurally by the presence of lamellar bodies and biochemically by an increase in SP-A content. Thus, EGF receptor is found in alveolar epithelium during differentiation, which suggests an important role for EGF during human fetal lung development.

Embryonic and Fetal Development↗

PubMedDate not supplied

In situ hybridization of SP-A mRNA in adult human conducting airways.

In our study, surfactant protein (SP)-A was characterized in adult human trachea and bronchi. SP-A mRNA and protein were localized to serous cells in submucosal gland by in situ hybridization and immunohistochemistry, respectively. A 2.2 kb SP-A mRNA transcript was detected in tracheal tissues by Northern blot analysis. Primer extension analysis and gene-specific reverse transcriptase polymerase chain reaction (RT-PCR) revealed the predominance of SP-A2 mRNA. However, using nested PCR, we also detected low amounts of SP-A1 mRNA in the tracheal tissues. A approximately 35 kDa SP-A immunoreactive protein was detected in the tracheal tissues by immunoblot analysis and was shown to be modified by the addition of N-linked oligosaccharides. We conclude that submucosal glands in the conducting airways produce a novel SP-A protein with a molecular weight and post-translational modification similar to the SP-A produced in the distal lung. We speculate that this SP-A2 protein, like other serous secretions from airway submucosal glands, functions in local antimicrobial host defense mechanisms in the conducting airways.

Adult↗

PubMedDate not supplied

Role of prolactin, cortisol, and insulin in the regulation of surfactant synthesis by the human fetal lung.

Cortisol, in combination with prolactin and/or insulin, increases the rate of lamellar body phosphatidylcholine synthesis and markedly increases the secretion of lamellar bodies into the ductular lumens of human fetal lung explants maintained in serum-free medium. This combination also alters glycerophospholipids of lamellar bodies formed in the explants to resemble surfactant secreted by the human fetal lung at term. The suggested inhibitory effect of insulin on surfactant synthesis by the fetal lung was not supported by this study.

Choline↗