Inhibitory receptor gp49B regulates eosinophil infiltration during allergic inflammation.
gp49B, an Ig-like receptor, negatively regulates the activity of mast cells and neutrophils through cytoplasmic immunoreceptor tyrosine-based inhibition motifs. To characterize the role of gp49B further 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 into the lung 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 degranulated mast cells was observed in RW-sensitized, gp49B-deficient mice, which had been challenged in the eye, as compared with C57BL/6 wild-type (WT) controls. Finally, an increase in allergic inflammation in the lungs of A. suum-infected, RW-sensitized mice was observed upon RW challenge, as compared with 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, 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.
Norris
Hillary H
HH
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Twinbrook II, 12441 Parklawn Drive, Rockville, MD 20852, USA.
Peterson
Mary E
ME
Stebbins
Chris C
CC
McConchie
Brittany W
BW
Bundoc
Virgilio G
VG
Trivedi
Shweta
S
Hodges
Marcus G
MG
Anthony
Robert M
RM
Urban
Joseph F
JF
Long
Eric O
EO
Keane-Myers
Andrea M
AM
D000485:Allergens; D031164:Ambrosia; D000818:Animals; D017165:Ascaris suum / Q000276:immunology / Q000502:physiology; D001985:Bronchial Provocation Tests; D015550:Cell Degranulation; D002469:Cell Separation; D003233:Conjunctivitis, Allergic / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004802:Eosinophilia / Q000276:immunology; D004804:Eosinophils / Q000276:immunology*; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology* / Q000469:parasitology; D007132:Immunoglobulin Isotypes / Q000097:blood; D007249:Inflammation / Q000276:immunology* / Q000469:parasitology; D008168:Lung / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008407:Mast Cells / Q000166:cytology / Q000502:physiology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010271:Parasites / Q000276:immunology / Q000502:physiology; D011971:Receptors, Immunologic / Q000276:immunology*
D000485:Allergens; D016207:Cytokines; D007132:Immunoglobulin Isotypes; C489448:Lilrb4 protein, mouse; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic