Hypersensitivity pneumonitis induced by the spore of Pleurotus Eryngii (Eringi).
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We reported the first case of hypersensitivity pneumonitis (HP) by an edible mushroom, Pleurotus Eryngii (Eringi). A 54-year-old woman had worked in a Bunashimeji mushroom factory for 42 months, and she moved to a new factory producing Eringi. Two months after, she was found to have HP by the spore of Eringi. Although no radiological finding was detected 6 months before the onset of HP, serum surfactant protein D (SP-D) had been elevated. We speculated that type II pneumocyte activation might prepare the ground for HP during the former exposure to Bunashimeji, and serum SP-D levels might reflect their conditions. (+info)
Detection and monitoring of methotrexate-associated lung injury using serum markers KL-6 and SP-D in rheumatoid arthritis.
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The applicability of monitoring concentrations of serum KL-6 and serum surfactant protein-D (SP-D) in the detection of methotrexate-associated lung injury (MTX pneumonitis) in patients with rheumatoid arthritis (RA) was investigated. The concentrations of these markers, sequentially measured in two patients with RA complicated with MTX pneumonitis, were increased in accordance with the severity of MTX pneumonitis. Conversely, the concentrations of these markers were decreased with the improvement of MTX pneumonitis, suggesting that the monitoring of these markers could be applicable not only for detecting the onset of MTX pneumonitis, but also for detecting the therapeutic response of MTX pneumonitis. (+info)
Reversibility of pulmonary abnormalities by conditional replacement of surfactant protein D (SP-D) in vivo.
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Surfactant protein D (SP-D) gene-targeted mice develop severe pulmonary disease associated with emphysema, pulmonary lipidosis, and foamy macrophage infiltrations. To determine the potential reversibility of these abnormalities, transgenic mice were developed in which SP-D was conditionally replaced in the respiratory epithelium of SP-D(-/-) mice. SP-D was not detected in the absence of doxycycline. Treatment with doxycycline after birth restored pulmonary SP-D concentrations and corrected pulmonary pathology at adulthood. When SP-D was replaced in adult SP-D(-/-) mice, alveolar SP-D was restored within 3 days, pulmonary lipid abnormalities were corrected, but emphysema persisted. In corrected adult SP-D(-/-) mice, loss of SP-D caused focal emphysema and pulmonary inflammation but did not cause phospholipid abnormalities characteristic of SP-D(-/-) mice. Thus, abnormalities in surfactant phospholipid homeostasis and alveolar macrophage abnormalities were readily corrected by restoration of SP-D. However, once established, emphysema was not reversed by SP-D. SP-D-dependent processes regulating surfactant lipid homeostasis were disassociated from those mediating emphysema. (+info)
Trimerization of the amino propeptide of type IIA procollagen using a 14-amino acid sequence derived from the coiled-coil neck domain of surfactant protein D.
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The folding of a collagen triple helix usually requires the presence of additional sequences that contribute to the association and correct alignment of the collagen chains. We recently reported that the C-terminal neck and lectin domains of a collagenous C-type lectin, rat pulmonary surfactant protein D (SP-D), are sufficient to drive the trimerization of a heterologous type IIA procollagen amino propeptide sequence. However, the conformation of the resulting trimeric IIA propeptide and the specific contributions of the SP-D sequence to trimerization were not elucidated. In the present study, we show that trimerization of the fusion protein is associated with correct folding of the collagen helix within the IIA propeptide domain (as assessed by circular dichroism) and that the constituent chains are hydroxylated. Chemical cross-linking and analytical ultracentrifugation showed that the IIA amino-propeptide retains its trimeric configuration even after proteolytic removal of the SP-D domains. By contrast, IIA amino-propeptides synthesized without fusion to the neck or lectin domains are assembled exclusively as monomers. To localize the trimerization sequence, mutant chimeric cDNA constructs were designed containing premature termination codons within the coiled-coil neck domain. A short, 14-amino acid sequence corresponding to the first two heptad repeats of the neck domain was sufficient to drive the trimeric association of the IIA amino-propeptide alpha-chains. However, deletion of the collagen domain resulted in the secretion of monomers. These studies demonstrate that two heptad repeats are sufficient for trimeric association of the propeptide but indicate that cooperative interactions between the coiled-coil and collagen domains are required for the formation of a stable helix. (+info)
Surfactant protein D reduces alveolar macrophage apoptosis in vivo.
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Surfactant protein D (SP-D) is a molecule of the innate immune system that recognizes the patterns of surface carbohydrate on pathogens and targets them for phagocytosis and killing. SP-D-deficient mice show an increased number of macrophages in the alveolar space, excess surfactant phospholipid, overproduction of reactive oxygen species, and the development of emphysema. We report here that SP-D-deficient mice have a 5- to 10-fold increase in the number of apoptotic and necrotic alveolar macrophages, as defined by annexin V and propidium iodine staining, respectively. Intrapulmonary administration of a truncated 60-kDa fragment of human recombinant SP-D reduces the number of apoptotic and necrotic alveolar macrophages and partially corrects the lipid accumulation in SP-D-deficient mice. The same SP-D fragment binds preferentially to apoptotic and necrotic alveolar macrophages in vitro, suggesting that SP-D contributes to immune homeostasis in the lung by recognizing and promoting removal of necrotic and apoptotic cells. (+info)
Surfactant protein D binds selectively to Klebsiella pneumoniae lipopolysaccharides containing mannose-rich O-antigens.
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Surfactant protein D (SP-D) plays important roles in the regulation of innate immune responses in the lung. We have previously shown that SP-D can agglutinate and enhance the macrophage-dependent killing of specific unencapsulated phase variants of Klebsiella pneumoniae. In the present studies, we used 16 clinical isolates of Klebsiella representing four O-serotypes and examined the interaction of SP-D with their isolated LPSs. Although SP-D bound to the core oligosaccharide of rough LPS from all isolates, it selectively bound to smooth forms of LPS expressed by O-serotypes with mannose-rich repeating units in their O-polysaccharides. SP-D was more potent in agglutinating unencapsulated phase variants of O-serotypes expressing these SP-D "reactive" O-polysaccharides, and more effectively inhibited the adhesion of these serotypes to lung epithelial cells. This novel anti-adhesion activity required the multimerization of trimeric SP-D subunits (dodecamers). Klebsiella serotypes expressing "nonreactive" LPS O-Ags were isolated at a significantly higher frequency from patients with K. pneumoniae. Our findings suggest that SP-D plays important roles in the clearance of opportunistic Gram-negative bacteria and contributes to known serotypic differences in the pathogenicity of Klebsiella through specific interactions with O-polysaccharides. (+info)
Intranasal delivery of a truncated recombinant human SP-D is effective at down-regulating allergic hypersensitivity in mice sensitized to allergens of Aspergillus fumigatus.
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C57BL/6 mice were sensitized to Aspergillus fumigatus 1-week culture filtrate, which is rich in the non-glycosylated allergen Asp f1, a major allergen in allergic bronchopulmonary aspergillosis (ABPA). A comparison of the effect of treatment of allergen challenged mice by intranasal administration of a 60-kDa truncated recombinant form of human SP-D (rfhSP-D) or recombinant full length SP-A (rhSP-A) was undertaken. Treatment with rfhSP-D produced significant reduction in IgE, IgG1 and peripheral blood eosinophilia and treatment with rfhSP-D, but not rhSP-A resulted in a significant reduction in airway hyperresponsiveness as measured by whole body plethysmography. Lung histology revealed less peribronchial lymphocytic infiltration in mice treated with rfhSP-D. Intracellular cytokine staining of spleen homogenates showed increases in IL-12 and IFN-gamma and decrease in IL-4. The level of endogenous mouse SP-D was elevated sixfold in the lungs of sensitized mice and was not affected by treatment with rfhSP-D. Taken with our previous studies, with a BALB/c mouse model of ABPA using a 3-week A. fumigatus culture filtrate, the present results show that rfhSP-D can suppress the development of allergic symptoms in sensitized mice independent of genetic background and using a different preparation of A. fumigatus allergens. (+info)
SP-D as a marker of amiodarone-induced pulmonary toxicity.
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Two patients with amiodarone-induced pulmonary toxicity (APT) showed abnormally increased serum SP-D concentrations, although their KL-6 level was within the normal range. In a 59-year-old man with ischemic heart disease, APT progressed rapidly and required steroid pulse therapy. During the clinical course, SP-D was as high as 375 ng/ml, although the KL-6 level was only 289 U/ml. In a 58-year-old man treated for dilated cardiomyopathy, SP-D increased to 289 ng/ml, while KL-6 remained at less than 500 U/ml. These cases indicate that SP-D is a useful and early diagnostic marker for APT even when KL-6 is not elevated. (+info)