title: Why does the autoantibody against granulocyte-macrophage colony-stimulating factor cause lesions only in the lung?
abstract: OBJECTIVE
  During the course of investigating the etiology of idiopathic pulmonary alveolar proteinosis (IPAP), the authors found that the autoantibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) was consistently present in both sera and the lung tissue. The autoantibody completely blocked bioactivity by direct binding with high specificity and avidity. Because of the existence of patients with congenital PAP who lack GM-CSF receptors and the development of PAP in GM-CSF and GM-CSF receptor knock-out mice, the autoantibody is likely to be the causative agent for IPAP. However, this finding posed the question as to why the autoantibody against GM-CSF caused lesions only in the lung.
  
  
  METHODS
  To answer this question, the authors investigated, using immunohistochemistry, confocal laser microscopy, and immunoblotting, the expression of PU.1 in tissue macrophages. PU.1 is a critical transcription factor for terminal differentiation of alveolar macrophage (AM), as reported previously in the lung, liver, spleen, kidney, intestine and brain.
  
  
  RESULTS
  PU.1 was consistently expressed in the nuclei of normal AM, but faintly or not at all in IPAP-AM. Moreover, it was not expressed in the nuclei of any other normal tissue macrophages tested. Blood monocytes expressed PU.1 in the cytosol but not in the nuclei. These results suggested that the differentiation pathway is different between AM and other tissue macrophages. PU.1 was not expressed in the nuclei of newborn rat lung AM but was gradually expressed during the first 10 days.
  
  
  CONCLUSIONS
  The authors demonstrated that GM-CSF is crucial for terminal differentiation of AM, but not for that of other tissue macrophages.
authors.affiliation: Bioscience and Medical Research Center, Niigata University Medical & Dental Hospital, Asahimachi-Dohri, Niigata, Japan. knak@med.niigata-u.ac.jp
authors.forename: Koh
authors.initials: K
authors.lastname: Nakata
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kanazawa
authors.forename: Masato
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001323:Autoantibodies; D016022:Case-Control Studies; D002454:Cell Differentiation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018613:Microscopy, Confocal; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism*; D011649:Pulmonary Alveolar Proteinosis / Q000276:immunology* / Q000473:pathology*; D051381:Rats; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D001323:Autoantibodies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1