JCI table of contents August 1, 2005

July 21, 2005

PHYSIOLOGY

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

AUTHOR CONTACT:
Mark T. Gladwin
NHLBI/NIH, Bethesda, MD USA
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

IMMUNOLOGY

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

AUTHOR CONTACT:
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

IMMUNOLOGY

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

AUTHOR CONTACT:
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

METABOLIC DISEASE

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

AUTHOR CONTACT:
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
-end-


JCI Journals

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