Lipoxin B4 promotes the resolution of allergic inflammation in the upper and lower airways of mice

• Published in: Mucosal immunology Vol. 8; no. 4; pp. 852 - 862
• Main Authors: Karra, L, Haworth, O, Priluck, R, Levy, B D, Levi-Schaffer, F
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-07-2015; Elsevier Limited
• Subjects: 631/250/347; 631/443/319; 692/699/1785; 692/699/249/2510/9; Allergology; Animals; Antibodies; Biomedical and Life Sciences; Biomedicine; Cell Degranulation - immunology; Chemotaxis, Leukocyte - immunology; Cytokines - metabolism; Disease Models, Animal; Eosinophils - immunology; Eosinophils - metabolism; Female; Gastroenterology; Immunoglobulin E - blood; Immunoglobulin E - immunology; Immunology; Inflammation - immunology; Inflammation - metabolism; Inflammation - pathology; Leukocytes - immunology; Leukocytes - metabolism; Leukocytes - pathology; Lipoxins - metabolism; Lung - immunology; Lung - metabolism; Lung - pathology; Male; Mast Cells - immunology; Mast Cells - metabolism; Mice; Mucus - metabolism; Nasal Mucosa - immunology; Nasal Mucosa - metabolism; Nasal Mucosa - pathology; Respiratory Hypersensitivity - immunology; Respiratory Hypersensitivity - metabolism; Respiratory Hypersensitivity - pathology
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/mi.2014.116

Chronic mucosal inflammation is the hallmark of important and common airway diseases, such as allergic rhinitis (AR) and asthma. Lipoxin A
4
(LXA
4
) is an endogenous pro-resolving mediator for mucosal inflammation that decreases allergic and asthmatic responses. Lipoxin B
4
(LXB
4
) is a structurally distinct member of the lipoxin family that signals in a manner distinct from LXA
4
. LXB
4
is generated by mucosal tissues, but its actions in allergic inflammation are unknown. Here, we used murine models of AR and asthma to investigate LXB
4
’s activity in mucosal inflammation. In the upper airway, LXB
4
significantly decreased nasal mucosal leukocytes and degranulation of mast cells (MCs) and eosinophils. In the lower airway, LXB
4
significantly decreased airway inflammation, mucus metaplasia, and hyper-responsiveness. Inhibition of MC degranulation
in vivo
by LXB
4
was more potent than dexamethasone, and these agents displayed unique profiles for cytokine regulation; however, their overall anti-inflammatory actions were comparable. LXB
4
decreased eotaxin-dependent eosinophil chemotaxis, IgE-mediated MC degranulation, and expression of type 2 cytokine receptors. Together, these findings indicate that LXB
4
carries cell type selective and mucosal protective actions that broaden the lipoxin family’s therapeutic potential for upper and lower airway catabasis.