Src homology 2 domain-containing inositol 5-phosphatase 1 deficiency leads to a spontaneous allergic inflammation in the murine lung

Sun Young Oh, Tao Zheng, Monica L. Bailey, Dwayne L. Barber, John Thomas Schroeder, Yoon Keun Kim, Zhou Zhu

Research output: Contribution to journalArticle


Background: Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP-1) controls the intracellular level of the phosphoinositide 3-kinase product phosphotidylinositol-3,4,5-trisphosphate and functions as a negative regulator of cytokine and immune receptor signaling. Emerging evidence suggests that the phosphoinositide 3-kinase pathway might be involved in allergic inflammation in the lung. However, the functional relevance of SHIP-1 in the TH2 activation pathway has not been established. SHIP-1-/- mice have spontaneous myeloproliferative inflammation in the lung, the nature of which has not been elucidated. We hypothesized that SHIP-1 plays an important role as a regulator in pulmonary allergic inflammation and in maintaining lung homeostasis. Objective: To test our hypothesis, we characterized the pulmonary phenotype of SHIP-1-/- mice. Results: Analyses of lung histopathology and bronchoalveolar lavage cellularity revealed that the majority of SHIP-1-/- mice had progressive and severe pulmonary inflammation of macrophages, lymphocytes, neutrophils, and eosinophils; mucous hyperplasia; airway epithelial hypertrophy; and subepithelial fibrosis. These pathologic changes were accompanied by exaggerated production of TH2 cytokines and chemokines, including IL-4, IL-13, eotaxin, and monocyte chemoattractant protein 1, in the lung. Furthermore, the number of mast cells significantly increased, and many of these cells were undergoing degranulation, which was correlated with increased content and spontaneous release of histamine in the lung tissue of SHIP-1-/- mice. Conclusion: These findings provide strong evidence that mice lacking SHIP-1 have an allergic inflammation in the lung, suggesting that SHIP-1 plays an important role in regulating the TH2 signaling pathway and in maintaining lung homeostasis. Clinical implications: SHIP-1 as a regulator might be a potential therapeutic target for controlling allergic inflammation in diseases such as asthma.

Original languageEnglish (US)
Pages (from-to)123-131
Number of pages9
JournalThe Journal of Allergy and Clinical Immunology
Issue number1
StatePublished - Jan 2007



  • allergy
  • asthma
  • Phosphatase
  • phosphoinositide 3-kinase
  • signaling
  • T2 inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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