Presence of c-KIT-positive mast cells in obliterative bronchiolitis from diverse causes.
BACKGROUND
The mechanism of fibrosis is not clear in patients with obliterative bronchiolitis after a remote injury. Immune-mediated progression may be a reason. c-KIT (CD117)-positive mast cells have been associated with chronic fibrosing diseases and may potentially be treated with imatinib (Gleevec), a c-KIT blocker.


OBJECTIVE
To evaluate the role of mast cells in fibrosis associated with obliterative bronchiolitis.


METHODS
Four cases of obliterative bronchiolitis (household cleaner exposure, ammonia exposure, idiopathic, and posttransplantation) were compared with asthma/emphysema. Small and large airways were stained for CD20, CD3, CD4, CD8, CD117, CD34, CD25, stem cell factor (c-KIT ligand) and with toluidine blue, hematoxylin-eosin, and trichrome. c-KIT (CD117)-stained slides were digitally scanned with Aperio ScanScope and stained cells within the epithelium and subepithelium of small and large airways were counted (per millimeter of basement membrane).


RESULTS
Mast cells were concentrated within the involved subepithelium of small airways in obliterative bronchiolitis (122 cells/mm), unlike asthma/emphysema (25 cells/mm). Conversely, there were more mast cells in the epithelium in cases of asthma/emphysema than in obliterative bronchiolitis (7 cells/mm and 2 cells/mm, respectively). Mast cells were significantly increased around involved airways versus uninvolved airways (52 cells/mm vs 14 cells/mm). Large airways in either group had similar c-KIT (CD117) expression. Stem cell factor was not increased.


CONCLUSIONS
Mast cells appear to be concentrated in the lesional small-airway subepithelium in obliterative bronchiolitis. The possible role of c-KIT inhibitors such as imatinib (Gleevec) in the progression of fibrosis preceding the development of obliterative bronchiolitis is discussed.
Fuehrer
Neil E
NE
Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
Marchevsky
Alberto M
AM
Jagirdar
Jaishree
J
D001249:Asthma / Q000378:metabolism; D001549:Benzamides; D015415:Biomarkers / Q000378:metabolism*; D055745:Bronchioles / Q000378:metabolism; D001989:Bronchiolitis Obliterans / Q000188:drug therapy / Q000378:metabolism*; D004646:Emphysema / Q000378:metabolism; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D000068877:Imatinib Mesylate; D008407:Mast Cells / Q000378:metabolism* / Q000473:pathology; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects / Q000378:metabolism*; D011743:Pyrimidines / Q000627:therapeutic use
D001549:Benzamides; D015415:Biomarkers; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit