Siglec-E is a negative regulator of acute pulmonary neutrophil inflammation and suppresses CD11b β2-integrin-dependent signaling

Sarah J McMillan, Ritu S Sharma, Emma J McKenzie, Hannah E Richards, Jiquan Zhang, Alan Prescott, Paul R Crocker (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    54 Citations (Scopus)

    Abstract

    Neutrophil entry into the lung tissues is a key step in host defense to bacterial and yeast infections, but if uncontrolled can lead to severe tissue damage. Here, we demonstrate for the first time that sialic acid binding Ig-like lectin E (siglec-E) functions to selectively regulate early neutrophil recruitment into the lung. In a model of acute lung inflammation induced by aerosolized lipopolysaccharide, siglec-E-deficient mice exhibited exaggerated neutrophil recruitment that was reversed by blockade of the ß2 integrin, CD11b. Siglec-E suppressed CD11b "outside-in" signaling, because siglec-E-deficient neutrophils plated on the CD11b ligand fibrinogen showed exaggerated phosphorylation of Syk and p38 mitogen-activated protein kinase. Sialidase treatment of fibrinogen reversed the suppressive effect of siglec-E on CD11b signaling, suggesting that sialic acid recognition by siglec-E is required for its inhibitory function. Siglec-E in neutrophils was constitutively associated with the tyrosine phosphatase SHP-1 and may therefore function to constitutively dampen inflammatory responses of neutrophils. These data reveal that siglec-E is an important negative regulator of neutrophil recruitment to the lung and ß2 integrin-dependent signaling. Our findings have implications for the human functional ortholog, siglec-9, and its potential role in regulating inflammatory lung disease.
    Original languageEnglish
    Pages (from-to)2084-2094
    Number of pages11
    JournalBlood
    Volume121
    Issue number11
    DOIs
    Publication statusPublished - 14 Mar 2013

    Keywords

    • Acute Disease
    • Animals
    • Antigens, CD
    • Antigens, CD11b
    • Antigens, CD18
    • Antigens, Differentiation, B-Lymphocyte
    • Cell Adhesion
    • Down-Regulation
    • Female
    • Male
    • Mice
    • Mice, Inbred C57BL
    • Mice, Knockout
    • Neutrophil Infiltration
    • Pneumonia
    • Signal Transduction

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