On the significance of Surfactant Protein-A within the human lungs (original) (raw)
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Expression and Localization of Lung Surfactant Protein A in Human Tissues
American Journal of Respiratory Cell and Molecular Biology, 2003
Lung surfactant protein A (SP-A) is a collectin produced by alveolar type II cells and Clara cells. It binds to carbohydrate structures on microorganisms, initiating effector mechanisms of innate immunity and modulating the inflammatory response in the lung. Reverse transcriptase-polymerase chain reaction was performed on a panel of RNAs from human tissues for SPA mRNA expression. The lung was the main site of synthesis, but transcripts were readily amplified from the trachea, prostate, pancreas, and thymus. Weak expression was observed in the colon and salivary gland. SPA sequences derived from lung and thymus mRNA revealed the presence of both SP-A1 and SP-A2, whereas only SP-A2 expression was found in the trachea and prostate. Monoclonal antibodies were raised against SPA and characterized. One of these (HYB 238-4) reacted in Western blotting with both reduced and unreduced SPA , with N-deglycosylated and collagenase-treated SPA , and with both recombinant SP-A1 and SP-A2. This antibody was used to demonstrate SPA in immunohistochemistry of human tissues. Strong SPA immunoreactivity was seen in alveolar type-II cells, Clara cells, and on and within alveolar macrophages, but no extrapulmonary SPA immunoreactivity was observed. In contrast to lung surfactant protein D (SP-D), which is generally expressed on mucosal surfaces, SPA seems to be restricted to the respiratory system. Lung surfactant protein A (SP-A) is a member of the collectin family, a group of oligomeric proteins in which a collagenous region is connected by an ␣-helical neck region to a C-type lectin or carbohydrate-recognition domain (CRD) (1-3). The structural subunit consists of three such polypeptide chains, and the functional protein is made up of six subunits linked by interchain disulfide bridges near the N-terminus (4). Post-translational modifications include complex N-linked glycosylation at Asn 187 in the CRD (4). Two genes encoding SPA transcripts, SP-A1 and SP-A2, are found in humans (2, 3, 5), and several alleles are known for each gene (6). Transcripts of both genes undergo
Surfactant proteins and the inflammatory and immune response in the lung
2009
Surfactant proteins are important for regulating surfactant activity and innate host defence; in particular, polymorphisms in intron 4 of the SP-B gene and dominant mutations of SP-C have been associated with bronchopulmonary dysplasia. The innate immune system is older and consists of soluble proteins, which bind microbial products and phagocytic leukocytes resembling primitive amebae, which float through the bloodstream and migrate into tissues at sites of inflammation, or reside in tissue waiting for foreign material. The innate immune system is always active and is immediately responsive, ready to recognize and inactivate microbial products entering lungs and other tissues. Pro-inflammatory cytokines (interleukins IL-1β, IL-6 and soluble ICAM-1) are present in lung lavage fluid from day 1 in premature infants with respiratory distress and reach a peak in the second week. IL-1β induces the release of inflammatory mediators, activating inflammatory cells and up-regulating adhesion...
Regularity of distribution of immunoreactive pulmonary surfactant protein A in rat tissues
International Journal of Molecular Medicine
Existing data has shown that SPA like protein or mRNA is widely distributed in lamellar bodies such as tissues and mucosal surfaces. Using immunohistochemistry method with a polyclonal antibody against human SPA , in this study we investigated distribution of immunoreactive pulmonary surfactant protein A (IR-SPA) in a number of rat tissues. The SPA like immunoreactivity was found in alveolar, parenchyma, pleura of lung; myelin sheath of brain; epithelia of Bowman's capsule, glomerulus and renal tubules of kidney; epithelia of colon, stomach, duct of salivary gland, pharynx; and blood vessel wall and connective tissue of extracellular matrix. The positive signal was blocked by pre-absorbed SPA antigen from recombinant or bronchoalveolar lavage (BAL). SPA has long been considered as an important frontier host defense molecule which participates in immune and inflammatory regulation of lung. With every inhalation, small particles, viruses, bacteria, and antigens from environment are continuously deposited onto the vast pulmonary epithelial surface. While a proper host defense is required to protect the lung, an over-exuberant response can disrupt the appropriate balance between pro-and anti-inflammatory. Traditional Chinese medicine believes that body is an open system relevant to the external environment. The physical, chemical and biological environmental factors constantly affect the open system, and the body properly reacts to maintain homeostasis of body machinery. The Chinese traditional medicine scholars have thus hypothesized that 'Qi' (meaning air) is the communication way between the body and external environment. What is 'Qi'? The results from our study suggest that IR-SPA is a candidate of 'Qi'. It is compatible with the sites, theoretically containing collagenous and lectin domain molecules, also compatible with the primary injury sites of some autoimmune diseases. SPA may be as one of 'Qi' molecules mentioned in traditional Chinese medicine that trigger some of autoimmune diseases.
The American journal of pathology, 1989
Newborn respiratory distress syndrome (RDS) results from a deficiency of pulmonary surfactant. Surfactant has three ultrastructural forms: lamellar bodies, which, when secreted from Type II pneumocytes, transform into tubular myelin; tubular myelin in turn gives rise to the phospholipid monolayer at the air-fluid interface in the alveolus that constitutes functional surfactant. It has been shown previously that the lungs of infants dying from RDS lacked tubular myelin despite the presence of abundant lamellar bodies, whereas the lungs of control infants dying from other causes had both tubular myelin and lamellar bodies. An abnormality in the conversion of lamellar bodies to tubular myelin in RDS was proposed as a possible explanation for this finding. To evaluate the role of surfactant proteins (SPs) in this conversion, the authors re-examined the lungs of 11 RDS infants and 10 control infants for reactivity with antisera to high and low molecular weight SPs. In control infants, ab...
The importance of surfactant on the development of neonatal pulmonary diseases
Clinics, 2007
Pulmonary surfactant is a substance composed of a lipoprotein complex that is essential to pulmonary function. Pulmonary surfactant proteins play an important role in the structure, function, and metabolism of surfactant; 4 specific surfactant proteins have been identified: surfactant proteins-A, surfactant proteins-B, surfactant proteins-C, and surfactant proteins-D. Clinical, epidemiological, and biochemical evidence suggests that the etiology of respiratory distress syndrome is multifactorial with a significant genetic component. There are reports about polymorphisms and mutations on the surfactant protein genes, especially surfactant proteins-B, that may be associated with respiratory distress syndrome, acute respiratory distress syndrome, and congenital alveolar proteinosis. Individual differences regarding respiratory distress syndrome and acute respiratory distress syndrome as well as patient response to therapy might reflect phenotypic diversity due to genetic variation, in part. The study of the differences between the allelic variants of the surfactant protein genes can contribute to the understanding of individual susceptibility to the development of several pulmonary diseases. The identification of the polymorphisms and mutations that are indeed important for the pathogenesis of the diseases related to surfactant protein dysfunction, leading to the possibility of genotyping individuals at increased risk, constitutes a new research field. In the future, findings in these endeavors may enable more effective genetic counseling as well as the development of prophylactic and therapeutic strategies that would provide a real impact on the management of newborns with respiratory distress syndrome and other pulmonary diseases.
Pulmonary surfactant-update on function, molecular biology and clinical implications
Current Respiratory Medicine Reviews
Departments of 1 Cellular and Molecular Physiology, 2 Pediatrics, and 3 Abstract: This review is based on the contents of an international congress entitled, "Surfactant 2004", organized by Drs. B. Lachmann and L.M.G. van Golde and held in Berlin, Germany. This is the fourth meeting of its kind; the first one was held in 1989. The purpose was to bring together investigators, interested in surfactant research from different disciplines to review progress in basic and clinical sciences, evaluate findings from clinical trials, and build upon the current knowledge to design better clinical trials for the prematurely born infant and other groups of patients, who are identified with surfactant dysfunction, as well as formulate new hypotheses for surfactant investigation both at the basic science and clinical science levels. Although the importance of surfactant in normal lung function was initially appreciated in the case of the prematurely born infant the importance of surfacta...
Molecular Endocrinology, 1987
We have examined the effect of explant culture and hormones on the major surfactant associated protein of M r 28,000-36,000 (SP 28-36) in human fetal lung. Explants of 16-to 23-week gestation lung were maintained for up to 5 days in culture. Polyclonal antibodies raised to SP 28-36 purified from alveolar proteinosis lung lavage were used in immunofluorescence experiments (n = 11). There was no specific fluorescence seen in frozen sections of preculture tissue. In explants cultured without serum or hormones, fluorescence was seen in most epithelial cells lining potential airspaces. In cultures treated with 10 riM dexamethasone and 2 nn/i T 3 much brighter fluorescence was seen in virtually all epithelial cells. Immunofluorescence studies on cell monolayers prepared from explants confirmed that SP 28-36 is found in the cytoplasm of type II cells but not in fibroblasts. The pattern of fluorescence was consistent with the presence of SP 28-36 on rough endoplasmic reticulum. SP 28-36 mRNA was measured in isolated cell populations using a 32 P-labeled cDNA probe. mRNA levels were manyfold higher in type II cell preparations (purity 78-92%) than in fibroblasts (purity 81-97%). A competitive enzyme linked assay was developed to quantify SP 28-36. The SP 28-36 content of five lungs before culture (17-23 weeks) was less
Molecular Genetics and Metabolism, 2009
Pulmonary surfactant is a complex mixture of phospholipids (PL) and proteins (SP) that reduce surface tension at the air-liquid interface of the alveolus. It is made up of about 70% to 80% PL, mainly dipalmitoylphosphatidylcholine (DPPC), 10% SPA , B, C and D, and 10% neutral lipids, mainly cholesterol. Surfactant is synthesized, assembled, transported and secreted into the alveolus where it is degraded and then recycled. Metabolism of surfactant is slower in newborns, especially preterm, than in adults. Defective pulmonary surfactant metabolism results in respiratory distress with attendant morbidity and mortality. This occurs due to accelerated breakdown by oxidation, proteolytic degradation, inhibition or inherited defects of surfactant metabolism. Prenatal corticosteroids, surfactant replacement, whole lung lavage and lung transplantation have yielded results in managing some of these defects. Gene therapy could prove valuable in treating inherited defects of surfactant metabolism.