Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The captive bubble tensiometer was employed to study interactions of phospholipid (PL) mixtures of dipalmitoylphosphatidylcholine (DPPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or 1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (POPG) at 50 microg/ml with physiological levels of the surfactant protein (SP) A SP-B, and SP-C alone and in combination at 37 degrees C. All surfactant proteins enhanced lipid adsorption to equilibrium surface tension (gamma), with SP-C being most effective. Kinetics were consistent with the presence of two adsorption phases. Under the conditions employed, SP-A did not affect the rate of film formation in the presence of SP-B or SP-C. Little difference in gamma(min) was observed between the acidic POPG and the neutral POPC systems with SP-B or SP-C with and without SP-A. However, gamma(max) was lower with the acidic POPG system during dynamic, but not during quasi-static, cycling. Considerably lower compression ratios were required to generate low gamma(min) values with SP-B than SP-C. DPPC-POPG-SP-B was superior to the neutral POPC-SP-B system. Although SP-A had little effect on film formation with SP-B, surface activity during compression was enhanced with both PL systems. In the presence of SP-C, lower compression ratios were required with the acidic system, and with this mixture, SP-A addition adversely affected surface activity. The results suggest specific interactions between SP-B and phosphatidylglycerol, and between SP-B and SP-A. These observations are consistent with the presence of a surface-associated surfactant reservoir which is involved in generating low gamma during film compression and lipid respreading during film expansion.
Am J Physiol Lung Cell Mol Physiol 2001 Jul
PMID:Surfactant protein interactions with neutral and acidic phospholipid films. 1140 66

This study examines the relationships between inflammation, surfactant protein (SP) expression, surfactant function, and lung physiology in a murine model of acute lung injury (ALI). 129/J mice received aerosolized endotoxin lipopolysaccharide [LPS] daily for up to 96 h to simulate the cytokine release and acute inflammation of ALI. Lung elastance (E(L)) and resistance, lavage fluid cell counts, cytokine levels, phospholipid and protein content, and surfactant function were measured. Lavage and lung tissue SP content were determined by Western blot and immunohistochemistry, and tissue messenger RNA (mRNA) levels were assessed by Northern blot and in situ hybridization. Tumor necrosis factor-alpha and neutrophil counts in bronchoalveolar lavage fluid increased within 2 h of LPS exposure, followed by increases in total protein, interleukin (IL)-1beta, IL-6, and interferon-gamma. E(L) increased within 24 h of LPS exposure and remained abnormal up to 96 h. SP-B protein and mRNA levels were decreased at 24, 48, and 96 h. By contrast, SP-A protein and mRNA levels and SP-C mRNA levels were not reduced. Surfactant dysfunction occurred coincident with changes in SP-B levels. This study demonstrates that lung dysfunction in mice with LPS-ALI corresponds closely with abnormal surfactant function and reduced SP-B expression.
Am J Respir Cell Mol Biol 2001 Jul
PMID:Decreased surfactant protein-B expression and surfactant dysfunction in a murine model of acute lung injury. 1147 73

The differential regulation of pulmonary surfactant proteins (SPs) is demonstrated in a murine model of Aspergillus fumigatus (Af )-induced allergic airway inflammation and hyperresponsiveness. BALB/c mice were sensitized intraperitoneally and challenged intranasally with Af extract. Enzyme-linked immunosorbent assay analysis of serum immunoglobulin (Ig) levels in these mice showed markedly increased total IgE and Af-specific IgE and IgG1. This was associated with peribronchial/perivascular tissue inflammation, airway eosinophilia, and secretion of interleukin (IL)-4 and IL-5 into the bronchoalveolar lavage fluid (BALF). Functional analysis revealed that in comparison with nonsensitized mice, allergic sensitization and challenge resulted in significant increases in acetylcholine responsiveness. To analyze levels of SPs, the cell-free supernate of the BALF was further fractionated by high-speed (20,000 x g) centrifugation. After sensitization and challenges, the pellet (large-aggregate fraction) showed a selective downregulation of hydrophobic SPs SP-B and SP-C by 50%. This reduction was reflected by commensurate decreases in SP-B and SP-C messenger RNA (mRNA) expression of the lung tissue of these animals. In contrast, there was a 9-fold increase in SP-D protein levels in the 20,000 x g supernate without changes in SP-D mRNA. The increased levels of SP-D showed a significant positive correlation with serum IgE (r = 0.85, P < 0.001). Tissue mRNA and protein levels of SP-A in either the large- or the small-aggregate fractions were unaffected. Our data indicate that allergic airway inflammation induces selective inhibition of hydrophobic SP synthesis accompanied by marked increases in the lung collectin SP-D protein content of BALF. These changes may contribute significantly to the pathophysiology of Af-induced allergic airway hyperresponsiveness.
Am J Respir Cell Mol Biol 2001 Jul
PMID:Aspergillus fumigatus-induced allergic airway inflammation alters surfactant homeostasis and lung function in BALB/c mice. 1147 74

The mechanisms whereby lung adaptation to hyperoxia occurs in the newborn period are incompletely understood. Pulmonary surfactant has been implicated in lung protection against hyperoxic injury, and elevated expression of certain surfactant proteins occurs in lungs of adult rats during adaptation to sublethal oxygen (85% O(2)). Here we report that newborn rats, which can adapt to even higher levels of hyperoxia (100% O(2)) than do adult rats, manifest changes in the lung surfactant proteins (SP), especially SP-A and SP-D. In newborn rats exposed to hyperoxia on Days 3 through 10 of life, lung messenger RNAs (mRNAs) for SP-A and SP-B gradually and progressively increased, relative to levels in age-matched, air-exposed newborns, over this 8-d period. By contrast, SP-C and SP-D mRNAs were maximally increased relative to values in simultaneously air-exposed control rats after 4 d of exposure. Lung mRNA for CC-10, a protein specific for Clara cells, was greater in hyperoxia-exposed rats than in air-exposed control rats on Day 4 of exposure, but not on other days. Lung mRNA for thyroid transcription factor (TTF)-1 was marginally increased on Days 1, 2, 4, and 6, and significantly increased on Day 8. Both SP-A and SP-D proteins were increased in lung lavage samples taken from hyperoxia-exposed newborns, relative to those taken from air-exposed controls, with the greatest increases occurring on Days 6 and 8 of exposure. However, the patterns of increase of the proteins were not identical to those of the respective mRNAs. In situ hybridization studies demonstrated increases in SP-D, and to a lesser extent in SP-A, in peripheral lung tissues from oxygen-exposed newborns. Taken together, these data indicate that specific surfactant proteins are upregulated at both the pretranslational and post-translational levels in distal lung epithelium during adaptation to hyperoxia in the newborn rat.
Am J Respir Cell Mol Biol 2001 Jul
PMID:Elevated expression of surfactant proteins in newborn rats during adaptation to hyperoxia. 1147 75

Although the lung is protected by classic innate and adaptive immune mechanisms, another unique local immunoregulatory system involving pulmonary surfactant is described in this review. Normal surfactant inhibits many immune cell functions including proliferation resulting from various stimuli and production of reactive oxidants, inflammatory mediators, and some cell surface markers. The predominant surfactant lipids appear to be responsible for these suppressive effects. Conversely, surfactant proteins SP-A and SP-D stimulate many aspects of immune cell behavior. These proteins are collagenous lectins or collectins that bind to glycoconjugates on many pathogens, enhancing phagocytosis and killing in some cases. SP-A and SP-D stimulate chemotaxis and reactive oxidant generation, particularly in macrophages, although other cells are probably affected as well. In some cases, SP-A also stimulates the expression of cell surface markers and is involved in the stimulation of inflammatory mediators. Under normal conditions, the inhibitory effects of the lipid prevail, but the collectins may provide focal activation and stimulate immune cells at sites where they are needed. However, in some types of lung disease or after certain insults or exposures, the balance between these inhibitory and stimulatory influences may be disrupted and result in inflammatory injury.
Pediatr Pathol Mol Med
PMID:Surfactant regulation of host defense function in the lung: a question of balance. 1148 34

Surfactant protein (SP) A and SP-D are members of the collectin superfamily. They are widely distributed within the lung, are capable of antigen recognition, and can discern self versus nonself. SPs recognize bacteria, fungi, and viruses by binding mannose and N-acetylglucosamine residues on microbial cell walls. SP-A has been shown to stimulate the respiratory burst as well as nitric oxide synthase expression by alveolar macrophages. Although nitric oxide (NO.) is a well-recognized microbicidal product of macrophages, the mechanism(s) by which NO. contributes to host defense remains undefined. The purpose of this symposium was to present current research pertaining to the specific role of SPs and reactive oxygen-nitrogen species in innate immunity. The symposium focused on the mechanisms of NO*-mediated toxicity for bacterial, human, and animal models of SP-A- and NO.-mediated pathogen killing, microbial defense mechanisms against reactive oxygen-nitrogen species, specific examples and signaling pathways involved in the SP-A-mediated killing of pulmonary pathogens, the structure and binding of SP-A and SP-D to bacterial targets, and the immunoregulatory functions of SP-A.
Am J Physiol Lung Cell Mol Physiol 2001 Sep
PMID:Lung surfactant and reactive oxygen-nitrogen species: antimicrobial activity and host-pathogen interactions. 1150 74

Surfactant protein (SP) A and SP-D are collectins that have roles in host defense. The Eustachian tube (ET) maintains the patency between the upper airways and the middle ear. Dysfunction of local mucosal immunity in ET may predispose infants to recurrent otitis media. We recently described preliminary evidence of the expression of SP-A and SP-D in the ET. Our present aim was to establish the sites of SP-A and SP-D expression within the epithelium of the ET in vivo. With in situ hybridization, electron microscopy, and immunoelectron microscopy, the cells responsible for SP-A and SP-D expression and storage were identified. SP-A expression was localized within the ET epithelium, and the protein was found in the electron-dense granules of microvillar epithelial cells. Being concentrated in the epithelial lining, only a few cells revealed intracellular SP-D, and it was not associated with granules. The SP-A and SP-D immunoreactivities in ET lavage fluid, as shown by Western blot analyses, were similar to those in bronchoalveolar lavage fluid. We propose that there are specialized cells in the ET epithelium expressing and secreting SP-A and SP-D. SP-A and SP-D may be important for antibody-independent protection of the middle ear against infections.
Am J Physiol Lung Cell Mol Physiol 2001 Sep
PMID:Surfactant proteins A and D in Eustachian tube epithelium. 1150 94

Intratracheal bleomycin in rats is associated with respiratory distress of uncertain etiology. We investigated the expression of surfactant components in this model of lung injury. Maximum respiratory distress, determined by respiratory rate, occurred at 7 days, and surfactant dysfunction was confirmed by increased surface tension of the large-aggregate fraction of bronchoalveolar lavage (BAL). In injured animals, phospholipid content and composition were similar to those of controls, mature surfactant protein (SP) B was decreased 90%, and SP-A and SP-D contents were increased. In lung tissue, SP-B and SP-C mRNAs were decreased by 2 days and maximally at 4--7 days and recovered between 14 and 21 days after injury. Immunostaining of SP-B and proSP-C was decreased in type II epithelial cells but strong in macrophages. By electron microscopy, injured lungs had type II cells lacking lamellar bodies and macrophages with phagocytosed lamellar bodies. Surface activity of BAL phospholipids of injured animals was restored by addition of exogenous SP-B. We conclude that respiratory distress after bleomycin in rats results from surfactant dysfunction in part secondary to selective downregulation of SP-B and SP-C.
Am J Physiol Lung Cell Mol Physiol 2001 Sep
PMID:Respiratory distress after intratracheal bleomycin: selective deficiency of surfactant proteins B and C. 1150 97

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.
Pediatr Pathol Mol Med
PMID:In situ hybridization of SP-A mRNA in adult human conducting airways. 1155 37

We report a simplified culture system for human fetal lung type II cells that maintains surfactant expression. Type II cells isolated from explant cultures of hormone-treated lungs (18-22 wk gestation) by collagenase + trypsin digestion were cultured on plastic for 4 days in serum-free medium containing dexamethasone (Dex, 10 nM) + 8-bromo-cAMP (0.1 mM + isobutylmethylxanthine (0.1 mM) or were untreated (control). Surfactant protein (SP) mRNAs decreased markedly in control cells between days 1 and 4 of culture, but mRNA levels were high in treated cells on day) 4 (SP-A, SP-B, SP-C, SP-D; 600%, 100%, 85%, 130% of day 0 content, respectively). Dex or cAMP alone increased SP-B, SP-C, and SP-D mRNAs and together had additive effects. The greatest increase in SP-A mRNA occurred with cAMP alone. Treated cells processed pro-SP-B and pro-SP-C proteins to mature forms and had a higher rate of phosphatidylcholine (PC) synthesis (2-fold) and higher saturation of PC (approximately 34% versus 27%) than controls. Only treated cells maintained secretagogue-responsive phospholipid synthesis. By electron microscopy, the treated cells retained lamellar bodies and extensive microvilli. We conclude that Dex and cAMP additively stimulate expression of surfactant components in isolated fetal type II cells, providing a simplified culture system for investigation of surfactant-related, and perhaps other, type II cell functions.
Pediatr Pathol Mol Med
PMID:Maintenance of differentiated function of the surfactant system in human fetal lung type II epithelial cells cultured on plastic. 1155 39


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