JCI table of contents August 1, 2005

July 21, 2005


The link between hemoglobin, NO production, and vasodilation

Hypoxic vasodilation is a fundamental physiological process that ensures that tissues receive adequate blood flow and oxygen delivery during respiration and metabolic stress. Although this process has been appreciated for many decades, the identity of the oxygen sensor and the mechanism of vasodilation remain uncertain.

In a study appearing online on July 21 in advance of print publication of the August 1 issue of the Journal of Clinical Investigation, Mark Gladwin and colleagues from the National Heart, Lung, and Blood Institute present biochemical data supporting a novel function for hemoglobin as a nitrite reductase, which generates nitric oxide (NO). Hemoglobin's enzymatic activity is highest when it is 40-60% saturated with oxygen, an ideal set point for NO generation during hypoxia. This proposed mechanism for NO formation is suited for regulating hypoxic vasodilation under a variety of physiological and pathological ranges of temperature and pH.

These studies support a novel role for hemoglobin and further unravel the mechanism of the nitrite-hemoglobin reaction. Understanding this chemistry may aid development of therapies that target NO delivery to tissues under hypoxic stress using nitrite solutions.

Title: Enzymatic Function of Hemoglobin as a Nitrite Reductase that Produces Nitric Oxide under Allosteric Control

Mark T. Gladwin
Phone: 301-435-2310; Fax: 301-451-7091; E-mail: mgladwin@mail.nih.gov

View the PDF of this article at: https://www.the-jci.org/article.php?id=24650


Biting into the mechanisms of oral tolerance

In a study appearing online on July 21 in advance of print publication of the August 1 issue of the Journal of Clinical Investigation, Lloyd Mayer and colleagues from Mt. Sinai School of Medicine demonstrate a novel model of tolerance induction in isolated loops of small bowel.

Previous studies have explored the role of M cells lining the intestinal surface, and Peyers patches (PPs), a subpopulation of dendritic cells present in the spleen, in oral tolerance induction. Contradictory data have evolved from such studies and studies like this are difficult since genetic manipulation or agents used to deplete M cells, PPs and lymph nodes affect the systemic immune system as well.

The present model uses immunologically intact mice with isolated loops of intestine that either contains PPs or M cells, or epithelial cells alone, in order to study the necessity for M cells and PP in mucosal tolerance. These segments of the bowel were accessible through an ostomy for antigen administration. Using this model the researchers show that M cells are not required for oral tolerance. These data provide the first in vivo evidence that epithelial cells can take up processed antigens and induce a regulated immune response.

Title: Mucosal tolerance induction in Peyer's Patch-deficient, ligated small bowel loops

Lloyd F. Mayer
Mount Sinai School of Medicine, New York, NY USA
Phone: 212-659-9266; Fax: 212-987-5593; E-mail: lloyd.mayer@mssm.edu

View the PDF of this article at: https://www.the-jci.org/article.php?id=19102


How bacteria break B cell tolerance

There is a lot of indirect evidence that microbial infections can initiate and/or worsen autoimmune disease. Autoantibody production during infection results from activation of low-affinity autoreactive B cells. But how this could lead to autoimmune disease is not clear.

In a study appearing online on July 21 in advance of print publication of the August 1 issue of the Journal of Clinical Investigation, Thierry Martin and colleagues from INSERM show in vivo that an experimental infectious disease creates the necessary and sufficient conditions to activate self-reactive B cells with significant affinity. This could drive them to mature into harmful memory B cells and lead to autoimmune diseases in susceptible individuals.

Title: Autoantigen, innate immunity and T cells cooperate to break B cell tolerance during bacterial infection

Martin Thierry
INSERM, Strasbourg, France
Phone: 33(0)390243983; Fax: 33(0)390244016; E-mail: thierry.martin@chru-strasbourg.fr

View the PDF of this article at: https://www.the-jci.org/article.php?id=24646


Understanding why a diet high in saturated fats is harmful

A diet that is high in saturated fat increases plasma cholesterol levels (LDL levels) and atherosclerosis. It was not known how dietary fats directly affect uptake of LDL cholesterol ester in the arteries and whether selective uptake was a factor. Selective uptake is a process whereby LDL cholesterol esters can be delivered to cell independent of the full LDL molecule.

In a study appearing online on July 21 in advance of print publication of the August 1 issue of the Journal of Clinical Investigation, Toru Seo and colleagues from Columbia University use mice that are resistant to atherosclerosis and those that are not to trace full LDL and LDL cholesterol ester uptake after being fed a high fat diet or a standard diet. The authors show that selective uptake contributes to LDL cholesterol ester delivery in both groups of mice, especially when they are fed the high fat diet. Selective uptake was also associated with increased plasma cholesterol and atherosclerosis. These results suggest that diet can influence delivery of LDL cholesterol ester to arteries via selective uptake, affecting cholesterol depostion and atherogenesis.

Title: Saturated fat diet enhances selective uptake of LDL cholesteryl esters in the arterial wall

Toru Seo
Columbia University, New York, NY USA
Phone: 212-305-3961; Fax: 212-305-3079; E-mail: ts227@columbia.edu

View the PDF of this article at: https://www.the-jci.org/article.php?id=24327

JCI Journals

Related Autoimmune Disease Articles from Brightsurf:

New insights into a potential target for autoimmune disease
With insights into a molecular pathway that regulates the activity of Tregs, a type of T cell involved in immunosuppression, research by the University of Pennsylvania's George Hajishengallis and colleagues opens up possibly new avenues for treating inflammatory and autoimmune diseases.

Research pinpoints rogue cells at root of autoimmune disease
Breakthrough cellular genomics technology has allowed Garvan and UNSW Sydney researchers to reveal genetic mutations causing rogue behaviour in the cells that cause autoimmune disease.

University of Alberta researchers discover new biomarker for rare autoimmune disease
University of Alberta researchers have identified a unique biological marker that can be used to identify the presence of the rare autoimmune disease myasthenia gravis, predict the course of the disease and identify new, personalized treatments.

Scientists discover autoimmune disease associated with testicular cancer
Using advanced technology, scientists at Chan Zuckerberg (CZ) Biohub, Mayo Clinic and University of California, San Francisco (UCSF), have discovered an autoimmune disease that appears to affect men with testicular cancer.

New proof that narcolepsy is an autoimmune disease
Researchers from the University of Copenhagen have discovered autoreactive cells in persons suffering from narcolepsy.

Novel treatments offer new hope for patients with autoimmune disease
Researchers at University of Utah Health have developed a new approach that targets the misfunctioning immune cells while leaving normal immune cells in place.

Undiplomatic immunity: Mutation causing arterial autoimmune disease revealed
Takayasu arteritis is an autoimmune disease resulting in chronic aortic inflammation leading to aneurysm or aortic regurgitation.

Immune checkpoints could be key to treating autoimmune disease myasthenia gravis
The PD-1 immune checkpoint is essential for self-recognition by the immune system, with disruption of the pathway associated with several autoimmune disorders.

Link between autoimmune, heart disease explained in mice
Autoimmune diseases such as psoriasis, lupus and rheumatoid arthritis more than double the risk of cardiovascular disease.

Organs are not just bystanders, may be active participants in fighting autoimmune disease
Findings from mouse study suggest organs affected by autoimmune disease suppress immune cells using methods similar to those used by cancer cells to evade detection.

Read More: Autoimmune Disease News and Autoimmune Disease Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.