The production of protective neutralizing antibodies occurs quickly in some viral infections but very slowly in others. In a new study, surface glycoproteins (the targets of neutralization) of 2 different viruses were genetically switched. Analysis of the neutralizing antibody response to each of the 2 parent and recombinant viruses in infected mice revealed that the speed of neutralizing antibody induction was intrinsically dependent on the surface glycoprotein and not the rest of the virus.
Eva Szomolanyi-Tsuda, Raymond M. Welsh
Retinitis pigmentosa is a heritable group of blinding diseases resulting from loss of photoreceptors, primarily rods and secondarily cones, that mediate central vision. Loss of retinal vasculature is a presumed metabolic consequence of photoreceptor degeneration. A new study shows that autologous bone marrow–derived lineage-negative hematopoietic stem cells, which incorporate into the degenerating blood vessels in two murine models of retinitis pigmentosa, rd1 and rd10, prevent cone loss. The use of autologous bone marrow might avoid problems with rejection while preserving central cone vision in a wide variety of genetically disparate retinal degenerative diseases.
Lois E.H. Smith
Members of the family of prostanoids, made up of prostaglandins and thromboxanes, are generated via COX-mediated metabolism of arachidonic acid. These lipid mediators exhibit wide-ranging biological actions that include regulating both vasomotor tone and renal sodium excretion. As COX inhibition is often associated with sodium retention leading to edema and hypertension, prostanoids appear to have a role in preventing the development of high blood pressure. On the other hand, prostaglandin E2 (PGE2) and PGI2 have also been implicated as determinants of renin secretion. A new study suggests that PGI2 plays a critical role in stimulating renin release and promoting hypertension following renal artery stenosis.
Helene Francois, Thomas M. Coffman
Finding mutations in nuclear genes responsible for disorders in the mitochondrial oxidative phosphorylation system has been a tedious matter. A “Venn diagram” approach — not unlike a classic complementation experiment — reported in this issue will now make the search easier.
Eric A. Schon
Vascularized organ transplants often fail because of smooth muscle cell migration and proliferation in the intima of graft arteries, leading to progressive lumenal narrowing and resultant ischemic damage. Graft arterial disease is caused by IFN-γ secreted by alloreactive T cells. New evidence indicates that IFN-γ dysregulates expression of the enzymes eNOS and iNOS in graft-infiltrating leukocytes. Dysregulated NO synthase expression occurs prior to and is causally linked to intimal smooth muscle cell accumulation.
Richard N. Mitchell, Andrew H. Lichtman
Glomerular filtration in the kidney is a continuous process that acts in concert with tubular reabsorption to prevent derangements of body fluid composition. Filtration is regulated by systemic factors, but it is also controlled by an intrinsic mechanism based on the anatomical connection between the distal nephron and the glomerular arterioles. Facing the threat of urinary salt loss, this mechanism causes vasoconstriction and reduces filtration by generating adenosine through the hydrolysis of nucleotide precursors such as 5′-AMP and possibly ATP .
Wilhelm Kriz
There is a wealth of clinical data showing the relationship between diabetes mellitus and atherosclerosis and its clinical complications. To dissect this relationship, investigators have attempted, usually unsuccessfully, to create a small-animal model in which diabetes accelerates vascular lesion development. This effort has often been complicated by development of hyperlipidemia leading to difficulty in differentiating the effects of hyperglycemia from those of lipid abnormalities. A study in the current issue of the JCI provides data on a new mouse model in which atherosclerosis initiation is accelerated in diabetic mice and is reduced by insulin therapy. Moreover, these animals have greater intra-arterial hemorrhage, which might be due to less stable plaques .
Ira J. Goldberg
Patients with systemic lupus erythematosus (SLE) often develop glomerulonephritis (i.e., inflammation in the glomeruli of the kidney), commonly referred to as lupus nephritis. Patients with lupus nephritis typically have autoantibodies to the complement classical pathway protein C1q. Whether these anti-C1q antibodies play any role in the development of lupus nephritis has been unclear. In this issue of the JCI, a new study demonstrates that anti-C1q antibodies can amplify glomerular injury but only when they are bound within the glomerulus to C1q that has been already brought to that site by other types of glomerular-reactive autoantibodies . These studies are the first, to our knowledge, to provide a causal link between anti-C1q antibodies and target organ damage in SLE.
V. Michael Holers
Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that is constitutively activated in a variety of human malignancies, including prostate, lung, brain, breast, and squamous cell carcinomas. Inhibition of activated Stat3 leads to decreased proliferation and apoptosis of many cancer-derived cell lines, while the introduction of a constitutively activated form of Stat3 into immortalized human breast epithelial cells and rodent fibroblasts results in cellular transformation. Collectively, these data suggest a role for Stat3 in oncogenesis. A new study from Chan et al. (see related article beginning on page 720) is the first to demonstrate a requirement for Stat3 in de novo epithelial carcinogenesis in vivo. Using the two-step model of chemically induced skin carcinogenesis, the authors demonstrated that mice deficient in Stat3 were completely resistant to skin tumor development.
Laura Pedranzini, Andrea Leitch, Jacqueline Bromberg
Pathological bone loss always reflects enhanced net osteoclastic activity. Recognition and binding of the receptor activator of NF-κB (RANK) by RANK ligand (RANKL) is the key osteoclastogenic event, and the signaling cascades induced by this reaction therefore contain potential anti-osteoporosis therapeutic targets. A study reported in this issue of the JCI documents that a pivotal component of RANKL/RANK-mediated osteoclast recruitment involves sequential induction of the transcription factors c-Jun and nuclear factor of activated T cells 2 .
Steven L. Teitelbaum
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