JCI table of contents: May 4, 2006


Halting histamine action means hallelujah for hay fever sufferers

In allergic diseases such as asthma, hay fever, and rhinitis an allergen stimulates the release of antibodies that attach themselves to mast cells causing these cells to release histamine, which can cause symptoms like itching of the nose, skin and eyes, sneezing, and wheezing. The characteristic "Th2 immune response" observed in allergy sufferers is an acquired immune response whose most prominent feature is high antibody production relative to the amount of cytotoxic T cells. Classical antihistamine drugs bind to but do not activate the histamine 1 receptor (H1R), subsequently blocking the allergic response. Interestingly, a recent study in Nature reported that mice deficient in H1Rs were still able to mount a Th2 immune response. In an effort to clarify this discrepancy, Paul Bryce and colleagues from Northwestern University, Chicago, examined H1R-/- mice with asthma and in their study appearing online on May 4 in advance of print publication in the June issue of the Journal of Clinical Investigation, these authors report a previously unknown role for H1R in the development of inflammatory airway responses. They found that these mice do indeed possess a dominant Th2 immune response to allergic antigens, yet they do not develop airway inflammation. Bryce et al. show that this is because the T cells in these mice are not able to travel to the site of allergen exposure – the lung. Histamine was found to act as an attractant for T cells and with no H1Rs present for histamine to bind to, the T cells were not recruited to the lung or able to cause the characteristic inflammatory allergic response in these mice. This advancement of our understanding of the roles of histamine in allergic disease indicates that blocking H1R with currently available drugs might have potential benefit for patients.

TITLE: The H1 histamine receptor regulates allergic lung responses

Paul J. Bryce
Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Phone: (312) 503-0077; Fax: (312) 503-0078; E-mail: [email protected].

View the PDF of this article at: https://www.the-jci.org/article.php?id=26150


Peptide inhibitor may prevent bone loss in osteoporosis

Two molecules known as RANK and TNFR promote the differentiation of osteoclasts – cells that are responsible for the breakdown of bone. This process occurs in healthy individuals – as part of the constant renewal of the bone that makes up our skeleton, and it occurs at an increased rate in individuals with diseases such as osteoporosis, rheumatoid arthritis, and periodontal disease. A site on TNFR that is critical for the binding of activating molecules is also conserved, in part, on RANK. In a study appearing online on May 4 in advance of print publication in the June issue of the Journal of Clinical Investigation, Roland Baron and colleagues from Yale University School of Medicine show that mimicking a critical loop of TNFR and RANK with a small cyclic peptide allows the inhibition of RANK ligand–induced bone breakdown and resorption in mouse models of osteoporosis. The authors used molecular modeling to demonstrate the exact region where the peptide binds and interferes with RANK signaling. These findings pave the way for the development of new strategies for designing peptide as well as nonpeptide inhibitors of RANK ligand–induced osteoclast-mediated bone loss, which is a key pathway in the mechanisms at work in many bone and joint diseases.

TITLE: A TNF receptor loop peptide mimic blocks RANK ligand–induced signaling, bone resorption, and bone loss

Roland Baron
Yale University School of Medicine, New Haven, Connecticut, USA.
Phone: (203) 785-5986; Fax: (203) 785-2744; E-mail: [email protected].

View the PDF of this article at: https://www.the-jci.org/article.php?id=22513


CEACAM1 is key for blood vessel growth in mice

The growth and remodeling of blood vessels occurs in adults by a process known as angiogenesis, and it can support the development and regeneration of organs as well as the progression of malignant diseases. Therefore the ability to be able to manipulate angiogenesis in disease is a highly desirable therapeutic option. A protein known as CEACAM1 (carcinoembryonic antigen–related cell adhesion molecule 1), which is expressed in newly formed blood vessels, had been previously shown to regulate the growth, maturation, and movement of mouse endothelial cells when grown in culture in the laboratory. In a study appearing online on May 4 in advance of print publication in the June issue of the Journal of Clinical Investigation, Christoph Wagener and colleagues from University Medical Center Hamburg-Eppendorf, Germany, now demonstrate that CEACAM1 expression is similarly important for the establishment of newly formed vessels in vivo in mice. They examined mice lacking CEACAM1 as well as mice in which CEACAM1 was only expressed by endothelial cells, which line blood vessels. Ceacam1-/- mice were unable to grow new capillaries in response to injury, whereas the mice expressing CEACAM1 only in their endothelial cells were able to do so. The results of this study suggest that CEACAM1 could be a future target for therapeutic manipulation of angiogenesis in disease states.

TITLE: Carcinoembryonic antigen–related cell adhesion molecule 1 modulates vascular remodeling in vitro and in vivo

Christoph Wagener
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Phone: 49-40-42803-2981; Fax: 49-40-42803-4621; E-mail: [email protected].

View the PDF of this article at: https://www.the-jci.org/article.php?id=24340


Last reviewed: By John M. Grohol, Psy.D. on 30 Apr 2016
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