Disease relevance of Sftpd

• NH(2)-rSftpa/d did not correct emphysema, foamy macrophage and lymphocyte infiltration, or the increased lipid accumulations characteristic of Sftpd(-/-) mice [1].
• Susceptibility of mice genetically deficient in the surfactant protein (SP)-A or SP-D gene to pulmonary hypersensitivity induced by antigens and allergens of Aspergillus fumigatus [2].
• SP-D deficiency results in multiple abnormalities in surfactant forms and metabolism that cannot be attributed to a single mechanism [3].
• Both serum and lung SP-D concentrations were increased in chronic lung inflammation [4].
• Since the airway is the usual portal of entry for influenza A virus and other respiratory pathogens, SP-D is likely to play an important role in innate defense responses to IAV [5].

Psychiatry related information on Sftpd

• The hydrophilic surfactant proteins A (SP-A) and D (SP-D) play important roles in host defense mechanisms of the lung [6].

High impact information on Sftpd

• Surfactant proteins A and D (SP-A and SP-D) are lung collectins composed of two regions, a globular head domain that binds PAMPs and a collagenous tail domain that initiates phagocytosis [7].
• The pulmonary collectins, surfactant proteins A (SP-A) and D (SP-D), have been reported to bind lipopolysaccharide (LPS), opsonize microorganisms, and enhance the clearance of lung pathogens [8].
• These data indicate that SP-A and SP-D are antimicrobial proteins that directly inhibit the proliferation of Gram-negative bacteria in a macrophage- and aggregation-independent manner by increasing the permeability of the microbial cell membrane [8].
• These results clearly implicate pulmonary SP-A and SP-D in the modulation of allergic reactions [9].
• Lung surfactant proteins SP-A and SP-D can interact with the glycosylated antigens and allergens of AFU:, inhibit specific IgE binding to these allergens, and block histamine release from sensitized basophils [9].

Chemical compound and disease context of Sftpd

• Pentoses, such as arabinose, ribose, and deoxyribose, inhibit the interaction between SP-D and mannan, one of the well-studied hexose ligands for SP-D, and biologically relevant d-forms of the pentoses are better competitors than the l-forms [10].
• CONCLUSION: These data suggest that SP-D not only reduces allergen-induced eosinophilic inflammation and airway hyperresponsiveness but also provides protection against early airway obstruction by inhibition of early mediator release [11].
• Role of surfactant protein D (SP-D) in innate immunity in the gastric mucosa: evidence of interaction with Helicobacter pylori lipopolysaccharide [12].

Biological context of Sftpd

• An NFAT-dependent enhancer modulated by NFATs or calcineurin and sensitive to cyclosporin was identified in the Sftpd promoter [13].
• Three new polymorphic microsatellites are also described, one of which is just 160 base pairs upstream of Sftpd [14].
• An atypical, rodent-specific, long terminal repeat of retroviral origin containing a minisatellite that has become inserted in Sftpd is described [14].
• The findings in the SP-D-deficient mice suggest a role for SP-D in surfactant homeostasis [15].
• On the basis of homology with other collectins, potential functions for SP-D include roles in innate immunity and surfactant metabolism [15].

Anatomical context of Sftpd

• Here, we identify a role of nuclear factor of activated T cells (NFATs) in regulation of murine SP-D gene (Sftpd) transcription [13].
• Nuclear factor of activated T cells regulates transcription of the surfactant protein D gene (Sftpd) via direct interaction with thyroid transcription factor-1 in lung epithelial cells [13].
• SP-D plays a critical role in the suppression of alveolar macrophage activation, which may contribute to the pathogenesis of chronic inflammation and emphysema [16].
• The SP-D gene was disrupted in embryonic stem cells by homologous recombination to generate mice deficient in SP-D [15].
• Surfactant protein D (SP-D) is one of two collectins found in the pulmonary alveolus [15].

Associations of Sftpd with chemical compounds

• In this study, we have examined the susceptibility of SP-A (AKO) or SP-D gene-deficient (DKO) mice to the Afu allergen challenge, as compared with the wild-type mice [2].
• Treatment with doxycycline after birth restored pulmonary SP-D concentrations and corrected pulmonary pathology at adulthood [17].
• Whereas no abnormalities were observed in SP-D (+/-) mice, alveolar and tissue phosphatidylcholine pool sizes were markedly increased in SP-D (-/-) mice [18].
• Antioxidants N-acetylcysteine and pyrrolidine dithiocarbamate inhibited MMP production by AMs from SP-D(-/-) mice [19].
• SP-D also enhanced tumor necrosis factor-alpha secretion by MM6 cells in response to purified lipopolysaccharide (LPS) isolated from the rough, but not the smooth, strains [20].

Physical interactions of Sftpd

• 1,3-beta-Glucan was a good stimulator of BAM for TNF-alpha production and was detected on B. dermatitidis by IFA. beta-Glucan incubated with BALF inhibited the binding of SP-D in BALF to B. dermatitidis as demonstrated by IFA [21].
• Increased NF-kappaB binding was detected by EMSA in nuclear extracts of AMs isolated from SP-D(-/-) mice [19].

Enzymatic interactions of Sftpd

• Alveolar macrophages of SP-D((-/-)) mice contained more nicked DNA than those of SP-A((-/-)) and wild type mice [22].

Regulatory relationships of Sftpd

• RESULTS: Following allergen exposure in vivo, SP-D(-/-) mice expressed higher BAL eosinophils and IL-13 concentrations and lower IFN-gamma expression at early time points compared with WT mice [23].

Other interactions of Sftpd

• The increased sCD14 seen in SP-D-/- mice was dependent upon the activation of MMP-12 via an MMP-9-dependent mechanism [24].
• In conclusion, SP-D influences innate host defense, in part, by regulating sCD14 in a process mediated by MMP-9 and MMP-12 [24].
• CD14 was reduced on alveolar macrophages from SP-D-/- mice and was associated with reduced uptake of LPS and decreased production of TNF-alpha after LPS stimulation [24].
• Whereas alveolar and tissue surfactant phospholipid pools were increased, levels of other surfactant proteins were not altered (SP-B) or were modestly increased (SP-A and SP-D) [25].
• Surfactant proteins-A and -D (SP-A and SP-D) are members of the collectin protein family [26].

Analytical, diagnostic and therapeutic context of Sftpd

• Soluble CD14 (sCD14) was increased in the bronchoalveolar lavage fluid from SP-D-/- mice [24].
• Human lung and stomach, but not heart or liver, were found to express SP-D mRNA, as determined by PCR [27].
• Northern blot and RT-PCR analysis revealed that the mouse SP-D gene is expressed predominantly in lung and, surprisingly, also in heart, stomach, and kidney but not in brain [27].
• Porcine SP-D will also be an important reagent for use in existing porcine animal models for human lung infections [28].
• Late isolates were shown to be much more sensitive than early strains to neutralization by the mouse serum mannose-binding lectin (MBL) and rat lung surfactant protein D (SP-D) and bound greater levels of these lectins in enzyme-linked immunosorbent assays and Western blot analyses [29].

References