Disease relevance of Sftpa1

• Lungs of SP-A (-/-) mice have markedly decreased tubular myelin figures and clear Group B streptococci and Pseudomonas aeruginosa less efficiently than SP-A wild type mice [1].
• In contrast, in the absence of SP-A, bacterial killing was decreased and associated with increased lung inflammation, decreased oxidant production, and decreased macrophage phagocytosis [2].
• The collectins, SP-A and SP-D, play distinct roles during bacterial infection of the lung [2].
• Mice lacking surfactant protein (SP)-A (SP-A-/-) or SP-D (SP-D-/-) and wild-type mice were infected with group B streptococcus or Haemophilus influenzae by intratracheal instillation [2].
• Cyclic AMP stimulation of expression of the SP-A-1766:hGH, SP-A-991:hGH, and SP-A-378:hGH fusion genes was limited to type II pneumonocytes in primary culture and was absent in two lung adenocarcinoma cell lines (NCl-H358 and A549), which do not express SP-A, and in cAMP-responsive adrenal Y1 cells [3].

Psychiatry related information on Sftpa1

• Dense-core plaques in Tg2576 and PSAPP mouse models of Alzheimer's disease are centered on vessel walls [4].

High impact information on Sftpa1

• After RSV infection, superoxide and hydrogen peroxide generation was deficient in macrophages from SP-A-/- mice, demonstrating a critical role of SP-A in oxidant production associated with RSV infection [5].
• Pulmonary infiltration with polymorphonuclear leukocytes was greater in the SP-A-/- mice [5].
• To determine the role of surfactant protein-A(SP-A) in antiviral host defense, mice lacking SP-A (SP-A-/-) were produced by targeted gene inactivation [5].
• SP-A, -B, and -C mRNAs were unaltered in lungs from GM-CSF-deficient and -replete mice [6].
• In this review we examine the evidence from in vitro systems and gene-targeted mice that two surfactant-associated collectins (SP-A and SP-D) may serve in these roles and help modify surfactant homeostasis as part of a coordinated host response to environmental challenges [7].

Chemical compound and disease context of Sftpa1

• Our results demonstrate that repeat exposure to inhaled endotoxin, either in the form of grain dust or purified LPS, results in increased whole lung SP-A gene expression and type II alveolar epithelial cell hyperplasia, whereas SP-A protein levels in lung lavage fluid are decreased [8].
• Chimeric gene(s) containing 1.8 kb of 5' SP-A sequences and the bacterial chloramphenicol acetyltransferase gene were expressed in pulmonary adenocarcinoma cells and in HeLa cells [9].
• We have initiated a study aimed at determining the effects of atorvastatin (Lipitor), a statin with the largest US market share, on brain A beta deposition in the PSAPP transgenic mouse model of Alzheimer's amyloidosis [10].
• Pulmonary edema and death caused by N-nitroso-N-methylurethane-induced lung injury were not different in SP-A(-/-) and SP-A(+/+) mice [11].

Biological context of Sftpa1

• Neither SP-A nor NH2-terminal domains of SP-A can substitute for SP-D in regulation of alveolar homeostasis [12].
• We suggest that SP-A secreted by the fetal lung serves as a hormone of parturition [13].
• Lung morphology, surfactant proteins B-D, lung tissue, alveolar phospholipid pool sizes and composition, and lung compliance in SP-A(-/-) mice were unaltered [14].
• Moreover, in vitro inhibition of sPLA(2)-IIA-induces surfactant phospholipid hydrolysis correlates with the concentration of SP-A in surfactant [15].
• Mutations of a putative cAMP-responsive element (TGACCTCA) at -261 bp revealed its functional importance in mediating cAMP regulation of SP-A gene expression [3].

Anatomical context of Sftpa1

• As surfactant protein A (SP-A), a member of the collectin family, inhibits LPS-induced in vitro IL-10 formation by bone marrow-derived macrophages, we studied its effect on MP under in vivo inflammatory conditions [16].
• The earlier phase (embryonic days 13-15; E13-E15) was characterized by CGRP, CC10, and SP-A immunostaining in all epithelial cells of the distal airways, with the three patterns being virtually identical in adjacent sections [17].
• These studies of SP-A (-/-) mice demonstrate that SP-A has an important role in the innate immune system of the lung in vivo [1].
• In the mouse, secretion of the major lung surfactant protein, surfactant protein A (SP-A), was first detected in amniotic fluid (AF) at 17 days postcoitum, rising progressively to term (19 days postcoitum) [13].
• The surfactant protein A (SP-A) gene was disrupted by homologous recombination in embryonic stem cells that were used to generate homozygous SP-A-deficient mice [14].

Associations of Sftpa1 with chemical compounds

• Tissue levels of saturated phosphatidylcholine were slightly reduced in the SP-A(-/-,rSP-A) mice compared with SP-A(-/-) littermates [18].
• Cyclic AMP analogs and glucocorticoids stimulate transcriptional activity of the SP-A gene in fetal rabbit lung tissue in culture; an additive effect is observed when the agents are added in combination [3].
• Wild-type and SP-A-deficient mice were conditioned with cyclophosphamide and lethal irradiation and then given allogeneic donor bone marrow plus inflammation-inducing spleen T cells [19].
• Using a murine model to mimic occupational exposures to endotoxin, we hypothesized that SP-A gene expression and protein would be elevated in response to repeat exposure to inhaled grain dust and to purified lipopolysaccharide (LPS) [8].
• Like surfactant protein A (SP-A), SP-D is a collagen-like glycoprotein belonging to the "collectin" class of C-type lectins that may play an important role in pulmonary host defense [20].

Enzymatic interactions of Sftpa1

• Alveolar macrophages of SP-D((-/-)) mice contained more nicked DNA than those of SP-A((-/-)) and wild type mice [21].

Regulatory relationships of Sftpa1

• Furthermore, intranasal administration of exogenous SP-A to mice with LPS-induced inflamed lungs led to a repression of the IL-10 production [16].
• Additionally, SP-A inhibited TNF-alpha stimulated by PMA in both wild-type and TLR4-mutant macrophages [22].
• These data suggest that SP-A inhibits inflammatory cytokine production in a CD14-independent manner and also by mechanisms independent of the LPS signaling pathway [22].

Other interactions of Sftpa1

• In normal mouse lung, the messenger RNAs (mRNAs) for SP-A, SP-B, and SP-D were expressed in both type II cells and Clara cells [23].
• In contrast to IL-10 production, SP-A concentrations during LPS-induced inflammation decreased with a nadir at Day 3, and then increased significantly within 24 h [16].
• SP-B and SP-C, but not SP-A, localized predominantly to the glycogen stores [24].
• Surfactant proteins-A and -D (SP-A and SP-D) are members of the collectin protein family [25].
• In addition, FGF-7 stimulates epithelial differentiation, stimulating expression of SP-A and SP-B mRNA throughout the explant, and inducing formation of focal areas of highly differentiated cells [26].

Analytical, diagnostic and therapeutic context of Sftpa1

• Mice lacking surfactant protein A (SP-A) mRNA and protein in vivo were generated using gene targeting techniques [1].
• SP-A mRNA and protein expression was detected in amniotic epithelial cells, chorionic trophoblasts and macrophages by in situ hybridization and immunohistochemistry [27].
• On Day 7 after BMT, bronchoalveolar lavage fluids from SP-A-deficient mice contained increased numbers of inflammatory cells and higher levels of proinflammatory mediators tumor necrosis factor-alpha, interferon-gamma, and nitric oxide than wild-type mice [19].
• Immunohistochemical staining of lung tissue and Western blot and enzyme-linked immunosorbent assay of lavage fluid showed marked increases in SP-A and SP-B in comparison with controls [28].
• Six hours after infection, bacterial counts were significantly higher in SP-A-/-, SP-D-/-, and SP-AD-/- compared with wild-type (WT) mice [29].

References