Evidence that granulocyte macrophage-colony-stimulating factor regulates the distribution and differentiated state of dendritic cells/Langerhans cells in human lung and lung cancers.
GM-CSF has been shown to be important for the survival and function of cells of dendritic cell/Langerhans cell (LC) lineage in vitro. Since these cells have been demonstrated to infiltrate human lung and some lung carcinomas, we hypothesized that the production of GM-CSF in the lung could be important in their recruitment and differentiation. Using both immunohistochemistry and in situ hybridization, we have shown that: (a) GM-CSF was produced by normal bronchiolar epithelium, the only site were CD1a+ LC are observed in the normal lung, whereas neither GM-CSF production nor LC were identified in normal alveolar epithelium. (b) In inflamed pulmonary tissue, hyperplastic alveolar cells produced GM-CSF, and CD1a+ LC accumulated adjacent to these cells. (c) Some, but not all, lung carcinomas produced this cytokine, and a close correlation was found between the production of GM-CSF and the number of CD1a+ LC infiltrating these tumors. Since GM-CSF was produced at all sites where CD1a+ LC are known to accumulate, but not at other locations within the lung, these data suggest that the local production of GM-CSF by certain lung cells may play an important role in determining the distribution and differentiated state of dendritic cell/LC in the human lung.
Tazi
A
A
Institut National de la Santé et de la Recherche Médicale (INSERM) U 82, Faculté de Médecine Xavier Bichat, Paris, France.
Bouchonnet
F
F
Grandsaigne
M
M
Boumsell
L
L
Hance
A J
AJ
Soler
P
P
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D018949:Antigens, CD1; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D007801:Langerhans Cells / Q000276:immunology*; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis
D015703:Antigens, CD; D018949:Antigens, CD1; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor