Research Briefs

Stem cells weave a web of hope Courtesy of Duncan Stewart University of Toronto investigators showed that injecting endothelial progenitor cells (EPCs) into the pulmonary circulation of rats results in microvasculature regeneration, a process they say might translate into therapy for pulmonary arterial hypertension. Current treatment of PAH, a rare but deadly disease of largely unknown origin, is merely palliative. Team leader Duncan Stewart says that research to date has missed the point by focusing on the larger pulmonary vessels rather than on the delicate web of capillaries that form the microcirculation. The team derived EPCs from stem cells of rat bone marrow. Three days following induction of experimental PAH with the toxic chemical monocrotaline, EPCs were injected directly into the pulmonary artery. "Our findings were striking," says Stewart. "Thirty days posttransplant, EPCs had migrated efficiently into the lungs and engrafted into the microvascular endothelium, repairing small arterioles and even capillaries." These microcirculatory changes, confirmed with fluorescence microangiography, were accompanied by functional improvements, including a 15-mmHg drop in pulmonary blood pressure. The group presented these results last month at the American Heart Association's Scientific Sessions in Orlando, Fla. Kurt Stenmark at the University of Colorado Health Science Center, Denver, calls the study "intriguing" but warns that the clinical relevance of the monocrotaline model should not be overstated. "The intervention was done when the endothelial injury was at its height; we never see patients at that stage," he says. It remains to be proven, he adds, that the transplanted EPCs had indeed engrafted and propagated in situ. --Joanna Lyford A b-Amyloid Masquerade Courtesy of The American Health Assistance Program German researchers recently strengthened the connection between inflammation and Alzheimer disease. Common pathogen structures such as lipopolysaccharide (LPS) signal their presence to a host by binding pattern-recognition receptors. This innate immunity is a powerful protector, but the discovery that the LPS receptor, CD14, also binds the Alzheimer hallmark peptide, b-amyloid (Ab),1 suggests that pattern recognition also may play a role in Alzheimer disease progression. It's a result that Klaus Fassbender, professor at the University of Göttingen, Germany, says "may have important therapeutic consequences." Fassbender and colleagues began work on CD14 and Alzheimer disease when they found that both LPS and Ab activated monocytes and microglial cells to similar levels. Fassbender's results revealed that CD14 can interact with Ab fibrils and that microglial inflammatory activation is reduced in CD14-deficient mice. Microglial inflammation is linked to Alzheimer neurodegeneration; this neurotoxicity, says Fassbender, is partly "mediated by a receptor for bacteria, the LPS receptor." Bruce Beutler, a professor at the Scripps Research Institute, La Jolla, Calif., says the finding, "if extended to its logical conclusion, has the potential to mean Alzheimer's is more of an inflammatory disease than people give it credit for." Therapeutic consequences of the research aren't yet clear, but further study into pattern-recognition receptors, such as the Toll-like receptors, says Beutler, could prove fruitful for the design of Alzheimer therapeutics. --David Secko 1. K. Fassbender et al., "The LPS receptor (CD14) links innate immunity with Alzheimer's disease," FASEB J, doi:10.1096/fj.03-0364fje, published online Nov. 3, 2003. Cellular Cleanup Courtesy of Robert T. Sauer When faulty protein translation litters the cell, tmRNA is the muscle behind the mop. If a ribosome becomes stuck while translating mRNA, two problems can arise: a ribosome that can't make new proteins, and a partially synthesized protein that could be deleterious if released in the cell. "tmRNA recognizes that stalled ribosome," explains Robert T. Sauer, professor of biology, Massachusetts Institute of Technology. Sauer and postdoc Christopher S. Hayes recently described a mechanism for translational quality control in bacteria.1 They purport that the ribosome stalling sets off a chain of events whereby the attached mRNA is cleaved, producing a unique ribosome-mRNA complex that lacks a 3' untranslated region. tmRNA, which shares features of both a transfer RNA and a messenger RNA, binds to the A site of this ribosome, adds a charged amino acid to the nascent protein chain, and enables translation of a tmRNA-encoded peptide tag that terminates with a normal stop codon. This allows normal disassembly of the ribosome-tmRNA complex, and protease degradation of the tagged incomplete protein. Kelly Williams, an assistant professor at Indiana University, Bloomington, who studies tmRNA structure, says that this paper finally provides a unified way to look at how tmRNA does its job. "It focuses our attention now on the mechanistic question...'How does tmRNA enter the ribosome in the first place?'" --Karen Kreeger 1. C.S. Hayes, R.T. Sauer, "Cleavage of the A site mRNA codon during ribosome pausing provides a mechanism for translational quality control," Mol Cell, 12:903-11, October 2003. function sendData() { document.frm.pathName.value = location.pathname; result = false if (document.frm.score[0].checked) result = true; if (document.frm.score[1].checked) result = true; if (document.frm.score[2].checked) result = true; if (document.frm.score[3].checked) result = true; if (document.frm.score[4].checked) result = true; if (!result) alert("Please select") return result; } b-Amyloid Masquerade; Cellular Cleanup"> b-Amyloid Masquerade; Cellular Cleanup"> .myradio{background-color : #94bee5} Please indicate on a 1 - 5 scale how strongly you would recommend this article to your colleagues? Not recommended 1 2 3 4 5 Highly recommended Please register your vote

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