Disease relevance of SFTPA1

• The effect of TNF alpha on SP-A content and mRNA in the pulmonary adenocarcinoma cell line, H441-4, was concentration and time dependent [1].
• Incubation of E. coli K12 with SP-A or SP-D increased bacterial permeability [2].
• In this study, we examined the effect of SP-A and SP-D on the growth and viability of Gram-negative bacteria [2].
• Furthermore, hypoxia caused a global increase in histone H3 dimethylated on Lys9 and increased the association of dimethyl histone H3 with the SP-A promoter [3].
• This study supports an important role of SP-A in controlling pulmonary inflammation caused by microbial pathogens [4].

Psychiatry related information on SFTPA1

• Pulmonary surfactant protein A (SP-A) plays an important part in Ab-independent host defense mechanisms of the lung [5].
• Here we characterize the chronological and spatial relationship of CLAC with other features of SP amyloid in the brains of patients with Alzheimer's disease (AD), Down syndrome (DS), and of PSAPP transgenic mice [6].
• At nanomolar SP-A concentrations, this complex is formed with a subsecond (0.3 s) reaction time, as measured by light-scattering signals evoked by photolysis of caged Ca(2+) [7].

High impact information on SFTPA1

• Upon recognition of the infectious agent, MBL and the ficolins initiate the lectin pathway of complement activation through attached serine proteases (MASPs), whereas SP-A and SP-D rely on other effector mechanisms: direct opsonization, neutralization, and agglutination [8].
• It has been known for several years that surfactant lipids suppress a variety of immune cell functions, most notably lymphocyte proliferation, which, conversely, is augmented by SP-A [9].
• On the C57BL/6J background, they develop a fatal disease characterized by pulmonary chronic interstitial inflammation and alveolar proteinosis, inflammation of the glandular stomach and skin resulting in scarring due to constant itching, and hyperplasia of lymphoid cells, haematopoietic cells and the forestomach epithelium [10].
• SPA1: a gene important for chromosome segregation and other mitotic functions in S. cerevisiae [11].
• Although steady-state hematopoiesis was unimpaired in homozygous mutant animals, all animals developed the progressive accumulation of surfactant lipids and proteins in the alveolar space, the defining characteristic of the idiopathic human disorder pulmonary alveolar proteinosis [12].

Chemical compound and disease context of SFTPA1

• Monocyte-derived macrophages on an SP-A substrate demonstrated enhanced pinocytosis of mannose BSA and phagocytosis of Mycobacterium tuberculosis lipoarabinomannan-coated microspheres [13].
• In the presence of calcium, a high-mobility complex of SP-A and [3H]Rb-LPS (Rb mutant of LPS from Escherichia coli strain LCD 25) micelles was formed, as detected by sucrose density gradients [14].
• It is concluded that SP-A acts via its sialic acid residues as an opsonin in the phagocytosis of influenza A virus by alveolar macrophages [15].
• The protective effects of intranasal administration of amphotericin B (AmB), human SP-A, SP-D and a 60-kDa fragment of SP-D (rSP-D) were examined in a murine model of invasive pulmonary aspergillosis (IPA) [16].
• In the present study, we investigated the hypothesis that SP-A is involved in bleomycin-induced pulmonary fibrosis [17].

Biological context of SFTPA1

• Finally, out of five intragenic haplotypes identified in the SFTPA1 gene and nine identified in the SFTPA2 gene, 1A ( 3 ) was most significantly associated with tuberculosis susceptibility (P=0.026) [18].
• In the present study, 88 infants with RDS and 88 control infants that were matched for degree of prematurity, prenatal glucocorticoid therapy, and sex were analyzed for SP-A genotypes [19].
• In this study, we found that O(2) also was permissive for IL-1 induction of SP-A expression and for cAMP and IL-1 stimulation of type II cell nuclear protein binding to the TBE [3].
• Cyclic AMP (cAMP) stimulation of SP-A expression in lung type II cells is O(2) dependent and mediated by increased phosphorylation and binding of thyroid transcription factor 1 (TTF-1) to an upstream response element (TTF-1-binding element [TBE]) [3].
• Surfactant protein A (SP-A), a major component of lung surfactant, participates in the innate immune response and can enhance phagocytosis [13].

Anatomical context of SFTPA1

• These studies provide further evidence that SP-A produced in the lung plays a role in modulating macrophage biology, thereby contributing to the alternative activation state of the alveolar macrophage [20].
• Based on ligand blot analysis, both type II cells and macrophages express a 210-kDa SP-A-binding protein [21].
• In the present report we have characterized the binding of surfactant protein A (SP-A) to bone marrow-derived macrophages, U937 cells, alveolar macrophages, and type II epithelial cells [21].
• We hypothesize that SP-A may serve a protective role in the lung by preventing C1q-mediated complement activation and inflammation along the delicate alveolar epithelium [22].
• Therefore, we proposed a role for SP-A in the conversion of lamellar bodies to tubular myelin and in the pathogenesis of RDS [23].

Associations of SFTPA1 with chemical compounds

• The newly expressed MR likely came from intracellular pools because: 1) up-regulation of the MR by SP-A occurred by 1 h, 2) new protein synthesis was not necessary for MR up-regulation, and 3) pinocytosis of mannose BSA via MR recycling was increased [13].
• We also found that exposure of mice to 90% O2 for 4 days, sufficient to lead to consumption of glutathione, oxidation of protein thiols, and accumulation of airspace protein-associated carbonyl moieties, blocked the permeabilizing activity of lavage fluid from SP-A+/+ mice [24].
• Activity at pH 7.4 was approximately 50% less, and inhibition by SP-A was partially dependent on Ca(2+) [25].
• SP-A also prevented C1q and C1 from binding to immune complexes [22].
• SP-A triggered the increase in cytosolic Ca2+ by inducing activation of phospholipase C, which leads to the hydrolysis of membrane phospholipids, yielding inositol 1,4,5-trisphosphate and mobilizing intracellularly stored Ca2+ by inositol triphosphate-sensitive channels [20].

Physical interactions of SFTPA1

• Glycoprotein-340 (gp-340) was first identified as a surfactant protein (SP)-D-binding molecule purified from lung lavage of patients with alveolar proteinosis (Holmskov, et al., J. Biol. Chem. 1997;272:13743) [26].
• We also determined whether specific SP-B variants interact with RDS susceptibility or protective SP-A variants to enhance or reduce risk for RDS [27].
• Surfactant-associated protein A (SP-A) is a component of pulmonary surfactant that binds to a specific receptor (SPAR) on the surface of type II alveolar cells of the lung and regulates gene expression and surfactant secretion [28].
• SP-A and SP-D also bind lipids and SP-A is involved in organization of alveolar surfactant phospholipids [29].
• To obtain a better understanding of how lung collectins modulate cellular responses, the authors investigated whether SP-A interacts with the toll-like receptor 2 (TLR2) [30].

Co-localisations of SFTPA1

• Microfibril-associated protein 4 binds to surfactant protein A (SP-A) and colocalizes with SP-A in the extracellular matrix of the lung [31].

Regulatory relationships of SFTPA1

• SP-A appeared to induce prostaglandin E(2) synthesis in chorionic trophoblasts via induction of cyclooxygenase type 2 expression [32].
• SP-A mRNA and protein are downregulated by phorbol esters (TPA) via inhibition of gene transcription [33].
• To test whether SP-A induced Smad signaling, a Smad3/4-specific reporter gene was transfected in primary human CD4(+) T lymphocytes [34].
• Because surfactant protein A (SP-A) is capable of modulating other functions of human monocytic cells, we hypothesized that SP-A may regulate MMP-9 expression [35].
• We speculate that SP-A may influence the protease/antiprotease balance in the lungs of patients with quantitative and/or qualitative changes in surfactant constituents favoring an abnormal breakdown of extracellular matrix components [35].

Other interactions of SFTPA1

• In the present study, we identified a GT box (GGGGTGGGG) at -61 bp of SP-A2 5'-flanking sequence that is highly conserved among the SP-A genes of different species [36].
• Cortisol (10(-7) and 10(-6) m, 24 h) induced SP-A expression in cultured chorionic trophoblasts, which could be blocked by the glucocorticoid receptor antagonist RU486 [32].
• Treatment of chorionic trophoblasts with SP-A (10-100 mug/ml, 24 h) caused a dose-dependent increase of prostaglandin E(2) release and an induction of cyclooxygenase type 2 but not cytosolic phospholipase A(2) and microsomal prostaglandin E synthase expression [32].
• In contrast to lung surfactant protein D (SP-D), which is generally expressed on mucosal surfaces, SP-A seems to be restricted to the respiratory system [37].
• RESULTS: At baseline, high levels of anti-GM-CSF antibodies and increased SP-A and SP-B levels were seen in all patients, and LDH was raised in 83% [38].

Analytical, diagnostic and therapeutic context of SFTPA1

• Concentrated bronchoalveolar lavage fluids from SP-A+/+ mice increased the permeability of the Escherichia coli K12 cell membrane to a greater extent than lavage from SP-A-/- animals [24].
• Design: SP-A expression was examined with immunohistochemistry and PCR [32].
• To further define the clinical relevance of SP-A aberrations, fluorescence in situ hybridization was done on both tumor cells and adjacent bronchial tissue cells from paraffin-embedded tissue blocks from 130 patients NSCLC for whom we had follow-up information [39].
• SP-A deletions might be a useful biomarker to identify poor prognoses in patients with NSCLC who might therefore benefit from adjuvant treatment [39].
• Measurement of SP-A in culture medium samples using single-step enzyme-linked immunosorbent assay showed a significant secretion of SP-A by isolated submucosal glands (1.2 +/- 0.08 ng/ml/h, SEM, n = 40) [40].

References