Three new human members of the lipid transfer/lipopolysaccharide binding protein family (LT/LBP)

Mulero, Julio J.; Boyle, Bryan J.; Bradley, Shannon; Bright, Jessica M.; Nelken, Sarah T.; Ho, Tam T.; Mize, Nancy K.; Childs, John D.; Ballinger, Dennis G.; Ford, J. E.; Rupp, Fabio

doi:10.1007/s00251-002-0467-3

Cited by 48 publications

(46 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…B is the negative control of A play an important role in adipose development. Fulllength SPLUNC1 protein was found to be structurally related to BPI, LBP, CETP, and PLTP (Guyard-Dangremont et al 1999;Mulero et al 2002;Zhou et al 2004). BPI and LBP were the bactericidal proteins and have the function of neutralizing the endotoxin.…”

Section: Resultsmentioning

confidence: 96%

“…Sequence and homology analyses suggest that SPLUNC1 is a member of the BPI/LBP family, with putative bactericidal/bacteriostatic function. Proteomics studies indicate that SPLUNC1 protein might be involved in irritant/inflammatory responses of the upper airways (Bingle and Craven 2002;LeClair 2003), the full-length SPLUNC1 protein was found to be structurally related to bactericidal permeability increasing protein (BPI), lipopolysaccharide-binding protein (LBP), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP) (Guyard-Dangremont et al 1999;Mulero et al 2002;Zhou et al 2004). BPI and LBP were the bactericidal protein and have the function of neutralizing the endotoxin.…”

Section: Introductionmentioning

confidence: 96%

See 1 more Smart Citation

Tissue distribution of the secretory protein, SPLUNC1, in the human fetus

Zhou

Fan

Zhao

et al. 2005

Histochem Cell Biol

View full text Add to dashboard Cite

We previously identified a tissue-specific gene, short palate, lung, and nasal epithelium clone 1 (SPLUNC1), in nasopharyngeal epithelial tissues. SPLUNC1 was differentially expressed in nasopharyngeal carcinoma. Bioinformatic analysis revealed that SPLUNC1 has the bactericidal permeability-increasing protein/lipid-binding protein (BPI/LBP) domain and a 19 amino acid signal peptide, which suggest that it is a secretory protein. Its precise cellular localization in the respiratory tract is mainly in mucous cells and ducts of submucosal glands. However, little is known about its expression pattern in various human tissues. We generated a highly specific antibody and analyzed its distribution in the human fetus by immunohistochemistry to more precisely determine SPLUNC1 protein localization in human tissues. The results were further validated by RT-PCR. Our results showed that SPLUNC1 protein is expressed at not only the serous glands and epithelium of the upper respiratory tract and digestive tract, but also in the oculi of human embryos. Interestingly, we also found positive staining in fetus adipose tissue, a result not previously reported in studies of adult human tissues. Western blot analysis detected a 24 kDa SPLUNC1 protein in the compounds of nasopharyngeal secretions. This secretory protein was also detected in saliva and tears. Our research suggests that SPLUNC1 protein may not only be an antimicrobial peptide that plays an important role in the maintenance of homeostasis in the upper respiratory tract, oculi, and alimentary tract, it may also be important in the development and lipid metabolism of the adipose tissue.

show abstract

Section: Resultsmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 96%

Tissue distribution of the secretory protein, SPLUNC1, in the human fetus

Zhou

Fan

Zhao

et al. 2005

Histochem Cell Biol

View full text Add to dashboard Cite

show abstract

“…The BPIL2 gene was found to be expressed in the basal cell layers of the epidermis in skin samples from psoriatic tissue. 88 However, little is known about the function of the BPIL2 protein. The avian homologue of the BPIL2 gene was recently shown to be highly expressed in the shell gland of mature but not of juvenile hens, pointing to a possible function in antimicrobial defence.…”

mentioning

confidence: 99%

“…Eight functional PLUNC homologues encoded in a single gene cluster on chromosome 20 in close proximity to the genes for BPI, LBP and PLTP are predicted to exist in humans. 88,90,91 The genes for the two other members, CETP and BPIL2, are located on Chromosomes 16 and 22 respectively. The PLUNC family can be divided in short (SPLUNC) and long (LPLUNC) proteins, the former consisting of only one domain corresponding to the LPSbinding N-terminal domain of BPI, the latter of two domains similar to full-length BPI.…”

mentioning

confidence: 99%

Antimicrobial peptides: The ancient arm of the human immune system

Wiesner¹,

Vilcinskas²

2010

Virulence

611

559

View full text Add to dashboard Cite

The production of peptides and small proteins with microbicidal activity collectively called antimicrobial peptides (AMPs) is commonly considered to be a primitive mechanism of immunity and has been extensively studied in insects and other non-vertebrate organisms. In addition, a variety of AMPs present in amphibian skin secretion has been well characterised. There is now increasing evidence that AMPs play a crucial role in human immunity as well. Virtually all human tissues and cells typically exposed to microbes are able to produce AMPs. Important AMPs belonging to two structurally distinct classes, known as the defensins and the cathelicidins, are mainly produced by epithelial cells and neutrophils. AMPs significantly contributing to the chemical skin barrier are represented by dermcidin, psoriasin and RNase 7. The antimicrobial activity of saliva largely depends on histidine-rich AMPs known as histatins. Many more, in part less well-known AMPs and AMP-like proteins exist that exhibit various additional functions, apart from their antimicrobial properties. Among them, the neutrophil granule proteins azurocidin and cathepsin G are members of a family of serine-protease homologues called serprocidins and play a role in the regulation of the immune response and degradation of extracellular matrix proteins respectively. As another AMP-like protein of the neutrophil granule content, bactericidal/permeability increasing protein (BPI) is both able to permeabilise bacterial membranes and to function as an opsonin. The whey acidic protein (WAP) domain containing class of AMPs, including secretory leukocyte protease inhibitor (SLPI), elafin and trappin-2, is equally important in inhibition of neutrophil serine proteases and killing of microbes. Certain CC or CXC chemokines are known to possess antimicrobial properties and therefore are called kinocidins. Several kinocidins, including thrombocidin-1 and -2, are contained in the ?-granules of platelets. A cytoplasmic AMP described as ubiquicidin turned out to be identical with the strongly basic ribosomal protein S30. Proteolytic cleavage of the histone protein H2A in the stomach gives rise to an AMP initially described as buforin I. Adrenomedullin is a hormone-like AMP exhibiting vasodilatory and hypotensive effects. Lysozyme is mainly known for its cell wall degrading activity, but is also capable of non-enzymatic killing of bacteria. An iron-binding protein present in milk and other secretions named lactoferrin was shown to possess antimicrobial and antiviral activity and has been implicated in protection against cancer. Clinical studies on the treatment of infectious diseases have been performed with artificial peptides derived from human lactoferrin, histatins and BPI in addition to porcine protegrins, frog magains and bovine indolicidin. Omiganan, representing an indolicidin derivative, has been demonstrated to be effective in the treatment of acne and catheter-related local infections and is currently considered to be the most promising AMP-based drug candidate

show abstract

“…We obtained two nrf-5 EST cDNAs from the C. elegans Genome Project and sequenced them to determine the intron-exon boundaries of F55B12.5 (see materials and methods). Using BLAST searches, we found that NRF-5 is homologous to four mammaliansecreted lipid-binding proteins: bactericidal permeabilityincreasing (BPI) protein (Gray et al 1989;Beamer et al 1997;Beamer 2003), lipopolysaccharide-binding protein (LBP; Fenton and Golenbock 1998;Iovine et al 2002;Mulero et al 2002), cholesteryl ester transfer protein (CETP; Bruce et al 1998a;Kawano et al 2000), and phospholipid transfer protein (PLTP; Huuskonen et al 1999;Vakkilainen et al 2002). These proteins have diverse functions, but share the ability to bind various lipids.…”

Section: Resultsmentioning

confidence: 99%

Fluoxetine-Resistance Genes inCaenorhabditis elegansFunction in the Intestine and May Act in Drug Transport

2006

View full text Add to dashboard Cite

Fluoxetine (Prozac) is one of the most widely prescribed pharmaceuticals, yet important aspects of its mechanism of action remain unknown. We previously reported that fluoxetine and related antidepressants induce nose muscle contraction of C. elegans. We also reported the identification and initial characterization of mutations in seven C. elegans genes that cause defects in this response (Nrf, nose resistant to f luoxetine). Here we present genetic evidence that the known nrf genes can be divided into two subgroups that confer sensitivity to fluoxetine-induced nose contraction by distinct pathways. Using both tissue-specific promoters and genetic mosaic analysis, we show that a gene from one of these classes, nrf-6, functions in the intestine to confer fluoxetine sensitivity. Finally, we molecularly identify nrf-5, another gene in the same class. The NRF-5 protein is homologous to a family of secreted lipid-binding proteins with broad ligand specificity. NRF-5 is expressed in the intestine and is likely secreted into the pseudocoelomic fluid, where it could function to transport fluoxetine. One model that explains these findings is that NRF-5 binds fluoxetine and influences its presentation or availability to in vivo targets.

show abstract

Three new human members of the lipid transfer/lipopolysaccharide binding protein family (LT/LBP)

Cited by 48 publications

References 27 publications

Tissue distribution of the secretory protein, SPLUNC1, in the human fetus

Tissue distribution of the secretory protein, SPLUNC1, in the human fetus

Antimicrobial peptides: The ancient arm of the human immune system

Fluoxetine-Resistance Genes inCaenorhabditis elegansFunction in the Intestine and May Act in Drug Transport

Contact Info

Product

Resources

About