The Journal of immunology (1950), 2003-12, Vol.171 (12), p.6866-6874
2003
Details
- Autor(en) / Beteiligte
- Titel
- IL-12 p40 homodimer-dependent macrophage chemotaxis and respiratory viral inflammation are mediated through IL-12 receptor beta 1
- Ist Teil von
- The Journal of immunology (1950), 2003-12, Vol.171 (12), p.6866-6874
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2003
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Leukocyte recruitment to the airway lumen is a central feature of inflammatory conditions such as asthma and respiratory viral infection. Characterization of mediators that regulate leukocyte recruitment in these conditions revealed increased IL-12 p40 homodimer (p80) levels were associated with enhanced airway macrophage accumulation. To examine this association, we used in vivo and in vitro assays to demonstrate p80, but not IL-12 or p40, provided a macrophage chemoattractant signal. Macrophages from genetically deficient mice indicated p80-dependent chemotaxis was independent of IL-12 and required IL-12Rbeta1 (Rbeta1) expression. Furthermore, analysis of murine cell lines and primary culture macrophages revealed Rbeta1 expression, with an intact cytoplasmic tail, was necessary and sufficient to mediate p80-dependent chemotaxis. To examine the role for Rbeta1 in mediating macrophage accumulation in vivo, we contrasted Sendai virus-driven airway inflammation in wild-type and Rbeta1-deficient mice. Despite similar viral burden and production of the macrophage chemoattractant p80, the Rbeta1-deficient mice displayed a selective decrease in airway macrophage accumulation and resistance to viral-dependent mortality. Thus, Rbeta1 mediates p80-dependent macrophage chemotaxis and inhibition of the p80-Rbeta1 interaction may provide a novel anti-inflammatory strategy to manipulate the inflammation associated with asthma and respiratory viral infection.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-1767eISSN: 1550-6606DOI: 10.4049/jimmunol.171.12.6866Titel-ID: cdi_proquest_miscellaneous_71447162
- Format
- –
- Schlagworte
- Animals, Antigens, CD - chemistry, Antigens, CD - physiology, Chemotactic Factors - chemistry, Chemotactic Factors - physiology, Chemotaxis - immunology, Cytoplasm - chemistry, Cytoplasm - genetics, Dimerization, Down-Regulation - genetics, Down-Regulation - immunology, Interleukin-12 - chemistry, Interleukin-12 - physiology, Interleukin-12 Subunit p40, Macrophages, Alveolar - immunology, Macrophages, Alveolar - pathology, Macrophages, Alveolar - virology, Macrophages, Peritoneal - cytology, Macrophages, Peritoneal - immunology, Macrophages, Peritoneal - metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, NIH 3T3 Cells, Protein Subunits - chemistry, Protein Subunits - physiology, Receptors, Interleukin - biosynthesis, Receptors, Interleukin - deficiency, Receptors, Interleukin - genetics, Receptors, Interleukin - physiology, Receptors, Interleukin-12, Receptors, Tumor Necrosis Factor - chemistry, Receptors, Tumor Necrosis Factor - physiology, Receptors, Tumor Necrosis Factor, Type II, Respiratory Tract Infections - genetics, Respiratory Tract Infections - immunology, Respiratory Tract Infections - pathology, Respirovirus Infections - genetics, Respirovirus Infections - immunology, Respirovirus Infections - pathology, Sendai virus - immunology, Sequence Deletion