Eosinophil infiltration in nonallergic chronic hyperplastic sinusitis with nasal polyposis (CHS/NP) is associated with endothelial VCAM-1 upregulation and expression of TNF-alpha.
We studied potential mechanisms of eosinophil accumulation in nonallergic chronic hyperplastic sinusitis with nasal polyposis (CHS/NP). We measured expression of endothelial vascular cell adhesion molecule-1 (VCAM-1), which mediates selective eosinophil transendothelial migration, the cytokines interleukin (IL)-1 beta, TNF-alpha and IL-13 which upregulate VCAM-1 expression, and the chemokine RANTES which mediates lymphocyte, monocyte, and eosinophil chemotaxis in chronic hyperplastic sinusitis with nasal polyposis (CHS/NP) nasal polyps (nonallergic versus allergic) and middle turbinate biopsies from normal controls. By immunohistochemical staining, the density of EG2+ eosinophils was increased in both the nonallergic and allergic CHS/NP subgroups compared to normal controls. VCAM-1 expression was significantly increased in CHS/NP subjects compared to normal controls (P = 0.0005), with the highest intensity seen in nonallergic CHS/NP. By in situ hybridization, the densities of IL-1 beta, TNF-alpha, IL-13, and RANTES mRNA+ cells were all increased in nonallergic CHS/NP compared to normal controls (P = 0.009, 0.0005, 0.0005, and 0.001, respectively). In comparison to allergic CHS/NP, nonallergic CHS/NP had a significantly higher tissue density of TNF-alpha (P = 0.04) and a lower density of IL-13 (P = 0.005) mRNA+ cells. In general, VCAM-1 expression correlated strongly in CHS/NP with the density of TNF-alpha (R = .91, P = 0.0005) but not the density of IL-1 beta, IL-13, or RANTES mRNA+ cells. We conclude that upregulation of VCAM-1 and elaboration of RANTES may contribute to the marked accumulation of eosinophils in nonallergic CHS/NP. TNF-alpha may play a critical role in VCAM-1 upregulation in this nonallergic eosinophilic disorder.
Hamilos
D L
DL
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Leung
D Y
DY
Wood
R
R
Bean
D K
DK
Song
Y L
YL
Schotman
E
E
Hamid
Q
Q
D000328:Adult; D000368:Aged; D001706:Biopsy; D002465:Cell Movement; D002908:Chronic Disease; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D004804:Eosinophils / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D012852:Sinusitis / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1