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51.
Phylogenetic and evolutionary analysis of the PLUNC gene family 总被引:7,自引:0,他引:7
Bingle CD LeClair EE Havard S Bingle L Gillingham P Craven CJ 《Protein science : a publication of the Protein Society》2004,13(2):422-430
The PLUNC family of human proteins are candidate host defense proteins expressed in the upper airways. The family subdivides into short (SPLUNC) and long (LPLUNC) proteins, which contain domains predicted to be structurally similar to one or both of the domains of bactericidal/permeability-increasing protein (BPI), respectively. In this article we use analysis of the human, mouse, and rat genomes and other sequence data to examine the relationships between the PLUNC family proteins from humans and other species, and between these proteins and members of the BPI family. We show that PLUNC family clusters exist in the mouse and rat, with the most significant diversification in the locus occurring for the short PLUNC family proteins. Clear orthologous relationships are established for the majority of the proteins, and ambiguities are identified. Completion of the prediction of the LPLUNC4 proteins reveals that these proteins contain approximately a 150-residue insertion encoded by an additional exon. This insertion, which is predicted to be largely unstructured, replaces the structure homologous to the 40s hairpin of BPI. We show that the exon encoding this region is anomalously variable in size across the LPLUNC proteins, suggesting that this region is key to functional specificity. We further show that the mouse and human PLUNC family orthologs are evolving rapidly, which supports the hypothesis that these proteins are involved in host defense. Intriguingly, this rapid evolution between the human and mouse sequences is replaced by intense purifying selection in a large portion of the N-terminal domain of LPLUNC4. Our data provide a basis for future functional studies of this novel protein family. 相似文献
52.
Apoptosis and the regulation of neutrophil lifespan 总被引:7,自引:0,他引:7
53.
A network of circuits, with KorB and TrbA as key regulators, controls genes for conjugative transfer of broad host range plasmid RK2. To assess the importance of the TrbA regulon, mutational analysis was applied to the TrbA operator at the trbB promoter and then to other TrbA-regulated promoters in the tra region. All identified TrbA operators are submaximal; in the case of trbBp, a G to A transition that made the operator core a perfect palindrome increased repression by about 50% compared to the wild type. When this change was introduced into the RK2 genome, decreases in transfer frequency of up to three orders of magnitude were observed, with bigger effects when Escherichia coli was the donor compared to Pseudomonas putida. Western blotting showed a significant decrease in Trb protein levels. These effects were much greater than the effect of the mutation on repression by TrbA alone. When KorB was introduced into the reporter system, the effects were closer to those observed in the whole RK2 context. These results indicate that co-operativity, previously observed between TrbA and KorB, allows big changes in transfer gene expression to result from small changes in individual regulator activities. 相似文献
54.
Induction of neutrophil apoptosis by the Pseudomonas aeruginosa exotoxin pyocyanin: a potential mechanism of persistent infection 总被引:6,自引:0,他引:6
Usher LR Lawson RA Geary I Taylor CJ Bingle CD Taylor GW Whyte MK 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(4):1861-1868
Pseudomonas aeruginosa colonizes and infects human tissues, although the mechanisms by which the organism evades the normal, predominantly neutrophilic, host defenses are unclear. Phenazine products of P. aeruginosa can induce death in Caenorhabditis elegans. We hypothesized that phenazines induce death of human neutrophils, and thus impair neutrophil-mediated bacterial killing. We investigated the effects of two phenazines, pyocyanin and 1-hydroxyphenazine, upon apoptosis of neutrophils in vitro. Pyocyanin induced a concentration- and time-dependent acceleration of neutrophil apoptosis, with 50 microM pyocyanin causing a 10-fold induction of apoptosis at 5 h (p < 0.001), a concentration that has been documented in sputum from patients colonized with P. aeruginosa. 1-hydroxyphenazine was without effect. In contrast to its rapid induction of neutrophil apoptosis, pyocyanin did not induce significant apoptosis of monocyte-derived macrophages or airway epithelial cells at time points up to 24 h. Comparison of wild-type and phenazine-deleted strains of P. aeruginosa showed a highly significant reduction in neutrophil killing by the phenazine-deleted strain. In clinical isolates of P. aeruginosa pyocyanin production was associated with a proapoptotic effect upon neutrophils in culture. Pyocyanin-induced neutrophil apoptosis was not delayed either by treatment with LPS, a powerfully antiapoptotic bacterial product, or in neutrophils from cystic fibrosis patients. Pyocyanin-induced apoptosis was associated with rapid and sustained generation of reactive oxygen intermediates and subsequent reduction of intracellular cAMP. Treatment of neutrophils with either antioxidants or synthetic cAMP analogues significantly abrogated pyocyanin-induced apoptosis. We conclude that pyocyanin-induced neutrophil apoptosis may be a clinically important mechanism of persistence of P. aeruginosa in human tissue. 相似文献
55.
Acceleration of human neutrophil apoptosis by TRAIL 总被引:15,自引:0,他引:15
Renshaw SA Parmar JS Singleton V Rowe SJ Dockrell DH Dower SK Bingle CD Chilvers ER Whyte MK 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(2):1027-1033
Neutrophil granulocytes have a short lifespan, with their survival limited by a constitutive program of apoptosis. Acceleration of neutrophil apoptosis following ligation of the Fas death receptor is well-documented and TNF-alpha also has a transient proapoptotic effect. We have studied the role of the death receptor ligand TRAIL in human neutrophils. We identified the presence of mRNAs for TRAIL, TRAIL-R2, and TRAIL-R3, and cell surface expression of TRAIL-R2 and -R3 in neutrophil populations. Neutrophil apoptosis is specifically accelerated by exposure to a leucine zipper-tagged form of TRAIL, which mimics cell surface TRAIL. Using blocking Abs to TRAIL receptors, specifically TRAIL-R2, and a TRAIL-R1:FcR fusion protein, we have excluded a role for TRAIL in regulating constitutive neutrophil apoptosis. No additional proapoptotic effect of leucine zipper TRAIL was identified following TRAIL treatment of neutrophils in the presence of gliotoxin, an inhibitor of NF-kappaB, suggesting TRAIL does not activate NF-kappaB in human neutrophils. TRAIL treatment of human neutrophils did not induce a chemotactic response. The susceptibility of neutrophils to TRAIL-mediated apoptosis suggests a role for TRAIL in the regulation of inflammation and may provide a mechanism for clearance of neutrophils from sites of inflammation. 相似文献
56.
Meléndez J Maldonado V Bingle CD Selman M Pardo A 《American journal of physiology. Lung cellular and molecular physiology》2000,278(4):L737-L743
Tissue inhibitors of metalloproteinases (TIMPs) play a key regulatory role in extracellular matrix remodeling. By screening a lung library with a human TIMP-2 cDNA probe, we have isolated the cDNA corresponding to guinea pig TIMP-2. The 3.5-kb cDNA presents an open reading frame that predicts a protein of 220 amino acids showing 97.2, 96.8, 97.2, and 77.3% overall identity with human, mouse, rat, and chicken TIMP-2, respectively. Guinea pig TIMP-2 cDNA was expressed in CHO-K1 cells, showing a protein with the expected molecular weight and activity. Northern blot analysis revealed TIMP-2 expression in brain, kidney, intestine, spleen, heart, and lung. Transforming growth factor-beta downregulated TIMP-2 mRNA in guinea pig lung fibroblasts, whereas a variety of other stimuli showed no effect. In normal and hyperoxia-exposed lungs, TIMP-2 mRNA was mainly localized in alveolar macrophages and epithelial cells. No quantitative differences were found by Northern blot. These results confirm that TIMP-2 is highly conserved in mammals and largely expressed in lungs. 相似文献
57.
Thyroid transcription factor-1 总被引:2,自引:0,他引:2
Colin D. Bingle 《The international journal of biochemistry & cell biology》1997,29(12):1471-1473
58.
Maslinda Musa Kirsty Wilson Le Sun Apoorva Mulay Lynne Bingle Helen M. Marriott Elizabeth E. LeClair Colin D. Bingle 《Cell and tissue research》2012,350(3):455-464
Despite being initially identified in mice, little is known about the sites of production of members of the BPI fold (BPIF) containing (PLUNC) family of putative innate defence proteins in this species. These proteins have largely been considered to be specificaly expressed in the respiratory tract, and we have recently shown that they exhibit differential expression in the epithelium of the proximal airways. In this study, we have used species-specific antibodies to systematically localize two members of this protein family; BPIFA1 (PLUNC/SPLUNC1) and BPIFB1 (LPLUNC1) in adult mice. In general, these proteins exhibit distinct and only partially overlapping localization. BPIFA1 is highly expressed in the respiratory epithelium and Bowman??s glands of the nasal passages, whereas BPIFB1 is present in small subset of goblet cells in the nasal passage and pharynx. BPIFB1 is also present in the serous glands in the proximal tongue where is co-localised with the salivary gland specific family member, BPIFA2E (parotid secretory protein) and also in glands of the soft palate. Both proteins exhibit limited expression outside of these regions. These results are consistent with the localization of the proteins seen in man. Knowledge of the complex expression patterns of BPIF proteins in these regions will allow the use of tractable mouse models of disease to dissect their function. 相似文献
59.
Kumaran Kandasamy Sujatha S Mohan Rajesh Raju Shivakumar Keerthikumar Ghantasala S Sameer Kumar Abhilash K Venugopal Deepthi Telikicherla Daniel J Navarro Suresh Mathivanan Christian Pecquet Sashi Kanth Gollapudi Sudhir Gopal Tattikota Shyam Mohan Hariprasad Padhukasahasram Yashwanth Subbannayya Renu Goel Harrys KC Jacob Jun Zhong Raja Sekhar Vishalakshi Nanjappa Lavanya Balakrishnan Roopashree Subbaiah YL Ramachandra Abdul B Rahiman Keshava TS Prasad Jian-Xin Lin Jon CD Houtman Stephen Desiderio Jean-Christophe Renauld Stefan N Constantinescu Osamu Ohara Toshio Hirano Masato Kubo Sujay Singh Purvesh Khatri Sorin Draghici Gary D Bader Chris Sander Warren J Leonard Akhilesh Pandey 《Genome biology》2010,11(1):1-9
60.