|URBAN JR, JOSEPH|
Submitted to: Journal of Leukocyte Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/5/2007
Publication Date: 12/21/2007
Citation: Norris, H., Peterson, M., Stebbins, C., Wetzel, B., Bundoc, V., Anthony, R., Urban Jr, J., Long, E., Keane-Myers, A. 2007. Infiltration of Neutrophils and Eosinophils during Allergic Inflammation is Regulated by the Inhibitory Receptor gp-49B. Journal of Leukocyte Biology. 82(6):1531-41.
Interpretive Summary: Disease interactions are often studied in mice because of the availability of reagents that can define both genetic and immunological characteristics of this species. The current study describes the evaluation of a regulatory molecule called gp49B that is normally found on the surface of inflammatory cells including mast cells, neutrophils, and eosinophils that are involved in the expression of allergic disease. The hypothesis that was tested was that the worm infection and allergens both stimulates components of the immune system that contribute to disease that becomes severe in the absence of regulatory molecules. It was observed that responses to the common roundworm, Ascaris suum, and the allergic response to ragweed were exacerbated in mice that were deficient in the cell surface receptor gp49B. The model is useful because it provides a marker on inflammatory cells that are important in the control of parasitic infection and allergic disease to gauge the level of host response. This observation can now be tested in host species of economic interest such as swine. This technology will be helpful to members of the scientific community that test substance with immune modulating activity that can be used to appropriately regulate immune function in livestock and man.
Technical Abstract: gp49B, an Ig-like receptor, negatively regulates the activity of mast cells and neutrophils through cytoplasmic immuno-receptor tyrosine-based inhibition motifs (ITIM). To further characterize the role of gp49B in vivo, gp49B-deficient mice were tested in two allergic models. Responses to ragweed (RW) challenge in the lung and conjunctiva were assessed in models of allergic inflammation, and during an infection with parasitic larvae of the nematode Ascaris suum. Infiltration by inflammatory cells during allergic responses was under negative control of the inhibitory receptor gp49B. Furthermore, an increase in conjunctival inflammation, with a predominance of eosinophils, neutrophils, and de-granulated mast cells, was observed in RW-sensitized gp49B-deficient mice that had been challenged in the eye, as compared to C57BL/6 wild type (WT) controls. Finally, an increase in allergic inflammation in the lungs of Ascaris suum–infected, RW-sensitized mice was observed upon RW challenge, as compared to C57BL/6 WT-controls. The observed influx of eosinophils into mucus membranes is characteristic of allergic asthma and allergic conjunctivitis, and may contribute to airway hyper-responsiveness (AHR), airway remodeling, and mucus production. Expression of gp49B was detected on peripheral eosinophils of control mice and on eosinophils from lungs of mice treated with RW, suggesting a role for gp49B on eosinophils in dampening allergic inflammatory responses.