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Query: UNIPROT:P06889 (Mol)
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The identification of genetic factors important in lung development and function will help in understanding the underlying molecular mechanisms of respiratory disease. Representational difference analysis of cDNA (cDNA-RDA) is a PCR-based subtractive enrichment procedure for the isolation of differentially expressed genes. We performed cDNA-RDA and isolated genes expressed more abundantly in fetal and adult lungs. Fifty-four clones potentially representing genes with higher transcript levels in the fetal lung were sequenced. Sequence similarity searches indicated that these clones included 12 known genes, a discoidin-like domain-containing gene, six expressed sequence tags (ESTs), and one novel sequence. Fifty-six clones potentially representing genes expressed more abundantly in the adult lung were also cloned and sequenced. Of these, 16 known human genes were represented along with two sequences significantly similar to known mouse genes and two novel sequences. Several of these known genes are implicated in stress response and lung protection. Thus cDNA-RDA was successfully used to isolate known and novel differentially expressed genes, which putatively play an important role in human lung development.
Am J Physiol Lung Cell Mol Physiol 2000 Feb
PMID:cDNA-RDA of genes expressed in fetal and adult lungs identifies factors important in development and function. 1066 12

Some serovars of Escherichia coli, mainly O2 and O78, are responsible for air sac and systemic infections in farm-raised turkeys (Meleagris gallopavo) and chickens (Gallus gallus). We looked in air sac surface fluid from young turkeys to identify proteins that bind surface polysaccharides of pathogenic respiratory E. coli O2. Turkey air sac surface fluid was subjected to affinity chromatography on Toyopearl AF-Epoxy-650M, coupled with either lipopolysaccharide (LPS) or lipid-free polysaccharide (LFP) purified from an avian pathogenic E. coli O2 isolate. A multimeric protein termed lipid-free polysaccharide binding protein-40 (LFPBP-40) composed of six covalently associated subunits of approximately 40 kDa was isolated by elution from LFP by EDTA or L-rhamnose. An analogous protein in air sac fluid proteins bound to intact E. coli O2 and eluted with L-rhamnose or N-acetylglucosamine (GlcNAc). The N-terminal amino acid sequence of LFPBP-40 DINGGGATLPQHLYLTPDV was related to the N-terminus of fragment 3 of a partially characterized human protein possessing T cell stimulation activity in synovial membrane of rheumatoid arthritis patients. However, endogenous amino acid sequences were unrelated to other known proteins. LFPBP-40 was immunoreactively distinct from pulmonary collectins and ficolins. These studies demonstrate a novel avian respiratory soluble lectin that can bind surface polysaccharides of pathogenic E. coli responsible for respiratory disease.
Comp Biochem Physiol B Biochem Mol Biol 2001 Oct
PMID:Avian air sac and plasma proteins that bind surface polysaccharides of Escherichia coli O2. 1156 92

The content-dependent activity of surfactant protein (SP)-B was studied in mixtures with dipalmitoyl phosphatidylcholine (DPPC), synthetic lipids (SL), and purified phospholipids (PPL) from calf lung surfactant extract (CLSE). At fixed SP-B content, adsorption and dynamic surface tension lowering were ordered as PPL/SP-B approximately SL/SP-B > DPPC/SP-B. All mixtures were similar in having increased surface activity as SP-B content was incrementally raised from 0.05 to 0.75% by weight. SP-B had small but measurable effects on interfacial properties even at very low levels < or =0.1% by weight. PPL/SP-B (0.75%) had the highest adsorption and dynamic surface activity, approaching the behavior of CLSE. All mixtures containing 0.75% SP-B reached minimum surface tensions <1 mN/m in pulsating bubble studies at low phospholipid concentration (1 mg/ml). Mixtures of PPL or SL with SP-B (0.5%) also had minimum surface tensions <1 mN/m at 1 mg/ml, whereas DPPC/SP-B (0.5%) reached <1 mN/m at 2.5 mg/ml. Physiological activity also was strongly dependent on SP-B content. The ability of instilled SL/SP-B mixtures to improve surfactant-deficient pressure-volume mechanics in excised lavaged rat lungs increased as SP-B content was raised from 0.1 to 0.75% by weight. This study emphasizes the crucial functional activity of SP-B in lung surfactants. Significant differences in SP-B content between exogenous surfactants used to treat respiratory disease could be associated with substantial activity variations.
Am J Physiol Lung Cell Mol Physiol 2002 Nov
PMID:Content-dependent activity of lung surfactant protein B in mixtures with lipids. 1237 40

Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is an important swine respiratory disease pathogen, which has at least 15 serotypes. There are several techniques for the serotyping of A. pleuropneumoniae, however, these techniques are time consuming. In this study, the polymerase chain reaction (PCR) technique was developed for serotyping A. pleuropneumoniae using a set of specific primer designated for the apxI, apxII, apxIII and apxIVA genes. By this PCR typing system, 10 out of the 13 reference strains of A. pleuropneumoniae were differentiated. However, it was not possible to distinguish serotype 2 from 8, serotype 5a from 5b and serotype 9 from 11. Each serotype of A. pleuropneumoniae showed its own products patterns. The PCR typing system was further applied for typing the field isolates of A. pleuropneumoniae and compared to that using the gel immunodiffusion (GID) technique. The results from both PCR and GID techniques were in accordance. Thus, the PCR typing system may provide a rapid and useful tool for typing the serotypes of A. pleuropneumoniae.
Mol Cell Probes 2003 Dec
PMID:Identification of the Actinobacillus pleuropneumoniae serotype using PCR based-apx genes. 1460 81

Cigarette smoking can lead to many human pathologies including cardiovascular and respiratory disease. Recent studies have defined a role for fibroblasts in the development of colon cancer. Moreover, fibroblasts are now thought of as key "sentinel" cells that initiate inflammation by releasing proinflammatory mediators including prostaglandins (PGs). Pathological overexpression of cyclooxygenase-2 (COX-2) and excess eicosanoid production are found in the early stages of carcinogenesis. By promoting chronic inflammation, COX-2 and eicosanoid production may actually cause a predisposition to malignancy. Furthermore, the associated inflammation induced by production of these mediators is central to the pathogenesis of chronic obstructive pulmonary disease. Little is known of the responses of normal lung fibroblasts to cigarette smoke, despite their abundance. We report herein that normal human lung fibroblasts, when exposed to cigarette smoke extract, induce COX-2 with concurrent synthesis of prostaglandin E2 (PGE2). The mechanisms by which cigarette-derived toxicants lead to increased COX-2 levels and PGE2 synthesis include increases in steady-state COX-2 mRNA levels (approximately four- to fivefold), phosphorylation of ERK1/2, and nuclear translocation of the p50 and p65 subunits of the transcription factor NF-kappaB, which are important elements in COX-2 expression. Furthermore, there was a dramatic 25-fold increase in microsomal prostaglandin E synthase, the key enzyme involved in the production of PGE2. We propose that normal human lung fibroblasts, when exposed to cigarette smoke constituents, elicit COX-2 expression with consequent prostaglandin synthesis, thus creating a proinflammatory environment. This chronic inflammatory state may act as one of the first steps towards epithelial transformation.
Am J Physiol Lung Cell Mol Physiol 2004 Nov
PMID:Cigarette smoke induces cyclooxygenase-2 and microsomal prostaglandin E2 synthase in human lung fibroblasts: implications for lung inflammation and cancer. 1523 7

The leukocyte integrins play a critical role in a great number of cellular adhesive interactions during the immune response. We describe here the isolation and characterization of the caprine beta(2) (CD18) sub-unit, common to the leukocyte beta(2)-integrin family. The deduced 770-amino-acid sequence reveals a transmembrane protein with 80, 81, 83, 96 and 99% identity with its canine, murine, human, bovine and ovine homologues respectively. Analysis of CD18 sequences emphasizes the functional importance of the beta(2) sub-unit I-like domain, and included metal ion-dependent adhesion site-like motif and confirms that of the cytoplasmic tail. Moreover, comparisons of ruminant versus non-ruminant CD18 sequences allowed the identification of 16 potential mutation sites that could be held responsible for the unique virulence of Mannheimia haemolytica for ruminants. Mannheimiosis is known to be the major respiratory disease among ruminants, whereas it is not pathogenic for other mammals, an observation that has been attributed to a specific interaction between M. haemolytica leukotoxin and ruminants' CD18. Therefore, the data provided here offer the possibility to explore new avenues in studies based on the caprine model and provide key information for future studies aimed at elucidating the molecular mechanisms underlying the ruminant-specific virulence of M. haemolytica.
Mol Membr Biol
PMID:Characterization of the caprine (Capra hircus) beta-2 integrin CD18-encoding cDNA and identification of mutations potentially responsible for the ruminant-specific virulence of Mannheimia haemolytica. 1551 36

Smoking cigarettes is a major risk factor for the development of cardiovascular and respiratory disease. Moreover, smoking-induced pathophysiology is often resistant to the anti-inflammatory effects of glucocorticoids. The nature of cigarette smoke-induced inflammation is still not defined, although neutrophil recruitment and activation seem to be consistent features. In the current study, we have used a range of approaches to demonstrate that cigarette smoke activates human monocytes and macrophages to release the CXC chemokine CXCL8 [(interleukin-8 (IL-8)]. Furthermore, we show for the first time that cigarette smoke synergizes with proinflammatory cytokines IL-1beta and tumor necrosis factor-alpha, and it is this interaction that confers steroid resistance to smoke-induced CXCL8 release. We go on to show that smoke-induced activation of human cells is an oxidant-mediated phenomenon acting through activator protein-1, but not nuclear factor kappaB, pathway. These observations add significantly to our understanding of smoke as an inflammatory stimulus that has implications for potential the development of treatments of smoking or related disease.
Mol Pharmacol 2005 Nov
PMID:Cigarette smoke activates human monocytes by an oxidant-AP-1 signaling pathway: implications for steroid resistance. 1606 72

A major cause of death and illness in children under the age of five, most living in polluted cities, is respiratory disease. Previous studies have shown that neonatal animals are more susceptible to bioactivated pulmonary cytotoxicants than adults, despite lower expression of the pulmonary cytochrome P-450s (CYP450s) thought to be involved in bioactivation. One CYP450 that is well documented in the bioactivation of many drugs and environmental toxicants in adult lung, but whose expression has not been evaluated during postnatal pulmonary development, is CYP450 3A (CYP3A). We compared age-specific expression of CYP3A1 in 7-day-old and adult male Sprague-Dawley rats. Unlike those shown for previously studied pulmonary CYP450s, expression levels for CYP3A1 mRNA in differentiating airway cells of postnatal rats are the same as in fully differentiated airway cells of adults. CYP3A1 protein expression (28%) and enzymatic activity (23%) were lower in postnatal airways compared with adults. Although other CYP450 immunoreactive proteins are primarily expressed in nonciliated cells, immunoreactive CYP3A1 protein was expressed in both ciliated and nonciliated cells in postnatal and adult rat proximal airways. CYP3A1 protein is detected diffusely throughout ciliated and nonciliated cells in 7-day-old rats, whereas it is only detected in the apex of these cells in adult rats. This study demonstrates that the lungs of postnatal rats have detectable levels of CYP3A1 and that CYP3A1 mRNA expression appears not to be age dependent, whereas steady-state CYP3A1 protein levels and enzyme activity show an age-dependent pattern.
Am J Physiol Lung Cell Mol Physiol 2006 Jul
PMID:Age-specific pulmonary cytochrome P-450 3A1 expression in postnatal and adult rats. 1646 30

Oxidative stress plays critical roles in initiation and/or worsening of respiratory disease process. Although reactive oxygen species (ROS) are shown to cause vascular leakage, the mechanisms by which ROS induce an increase in vascular permeability are not clearly understood. In this study, we have used a murine model to evaluate the effect of hydrogen peroxide (H(2)O(2)) to examine roles of ROS and the molecular mechanism in vascular permeability. The results have revealed that ROS levels, vascular endothelial growth factor (VEGF) expression, hypoxia-inducible factor-1alpha protein level, airway hyperresponsiveness, and vascular permeability are increased after inhalation of H(2)O(2). Administration of antioxidants markedly reduced plasma extravasation and VEGF levels in lungs treated with H(2)O(2). These results indicate that ROS may modulate vascular permeability via upregulation of VEGF expression.
Am J Respir Cell Mol Biol 2006 Aug
PMID:Hydrogen peroxide induces vascular permeability via regulation of vascular endothelial growth factor. 1657 43

Immune-mediated lung injury is an important component of Pneumocystis pneumonia (PcP)-related immunorestitution disease (IRD). However, the individual contribution of CD4(+) and CD8(+) T cells to the pathophysiology of IRD remains undetermined. Therefore, IRD was modeled in severe combined immunodeficient mice, and specific T cell depletion was used to determine how T cell subsets interact to affect the nature and severity of disease. CD4(+) cells were more abundant than CD8(+) cells during the acute stage of IRD that coincided with impaired pulmonary physiology and organism clearance. Conversely, CD8(+) cells were more abundant during the resolution phase following P. carinii clearance. Depletion of CD4(+) T cells protected mice from the acute pathophysiology of IRD. However, these mice could not clear the infection and developed severe PcP at later time points when a pathological CD8(+) T cell response was observed. In contrast, mice depleted of CD8(+) T cells efficiently cleared the infection but developed more severe disease, an increased frequency of IFN-gamma-producing CD4(+) cells, and a prolonged CD4(+) T cell response than mice with both CD4(+) and CD8(+) cells. These data suggest that CD4(+) T cells mediate the acute respiratory disease associated with IRD. In contrast, CD8(+) T cells contributed to neither lung injury nor organism clearance when CD4(+) cells were present, but instead served to modulate CD4 function. In the absence of CD4(+) cells, CD8(+) T cells produced a nonprotective, pathological immune response. These data suggest that the interplay of CD4(+) and CD8(+) T cells affects the ultimate outcome of PcP-related IRD.
Am J Physiol Lung Cell Mol Physiol 2006 Dec
PMID:Contribution of T cell subsets to the pathophysiology of Pneumocystis-related immunorestitution disease. 1689 94


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