Intercellular adhesion molecule-1 expression in activated eosinophils is associated with mucosal remodeling in nasal polyps

Abstract

Nasal polyposis (NP) is characterized by chronic mucosal inflammation with infiltrating eosinophils. Eosinophil‑mediated tissue remodeling may be involved in NP pathogenesis; therefore, improved understanding of tissue remodeling may result the identification of novel pathways and therapeutic strategies. The present study aimed to investigate the pathological changes occurring during tissue remodeling in NP, in order to assess the role of intercellular adhesion molecule‑1 (ICAM‑1) in localized tissue remodeling and the potential association between ICAM‑1 expression and markers of eosinophil activation. A total of 28 eligible patients and 10 healthy controls participated in the current study. Nasal mucosal tissues of these subjects were retrospectively evaluated for mucosal remodeling using histopathological staining. ICAM‑1 and eosinophil cationic protein (ECP) expression levels were determined by immunohistochemical analysis. Compared with the healthy controls, all the specimens from NP patients presented substantial epithelial damage, skewed cellular distribution with a reduced density of goblet cells, an increased density of subepithelial gland and increased subepithelial collagen deposition. In addition, the NP specimens exhibited significantly higher eosinophil infiltration and ICAM‑1 expression compared with the controls. Positive correlations were observed between ICAM‑1 and ECP expression levels (P=0.010), as well as between extracellular collagen deposition and ICAM‑1 (P=0.010) and ECP (P=0.012) expression levels in the NP specimens, but not in the control specimens. Morphological evidence demonstrated eosinophil‑mediated tissue remodeling in NP tissues. ICAM‑1 expression in activated eosinophils was associated with NP remodeling, indicating the possibility that ICAM‑1 may regulate NP remodeling.

Figure 1

Histopathological characteristics of epithelial damage of nasal mucosa and thickening of the basement membrane was assessed in hematoxylin and eosin stained sections using the following staging system: (A) Stage 0, normal epithelium (arrow) and basement membrane; (B) stage 1, cilia loss (arrow) and basement membrane thickening; (C) stage 2, eroded epithelium (arrow), thickening basement membrane and intact basal layer; and (D) stage 3, complete erosion (arrow) of the epithelium and massive thickening of the basement membrane (magnification, ×400). (E) Percentage of NP and control specimens observed at each stage. The percentage of NP specimens exhibiting stage 3 epithelial damage indicative was significantly greater compared with the control group (P=0.005). The control group exhibited more intact epithelia or mild epithelial shedding (stage 0) compared with the NP group (P=0.030). NP, nasal polyposis.

Figure 2

Distribution of goblet cells and subepithelial glands in NP and control nasal mucosa specimens. Alcian blue-periodic acid-Schiff staining revealed the presence of (A) clusters of subepithelial hyperplasia glands (arrows) that were distributed asymmetrically in the NP specimens (magnification, ×400) and (B) normal mucosa with pseudostratified columnar ciliated epithelium and scattered goblet cells (arrows) in the control specimens (magnification, ×400).(C) Densities of goblet cells and subepithelial glands in NP and control specimens. NP, nasal polyposis.

Figure 3

Histopathological characteristics of collagen deposition in the mucosal epithelium of NP and control nasal mucosa specimens, observed using Masson’s trichrome staining. (A) The basement membrane thickness (P=0.010), collagen deposition in the mucosal epithelium (P=0.030) and collagen thickness within the subepithelial layer (P=0.001) differed significantly between the NP and control groups. (B) Normal nasal mucosa of the control group exhibiting an intact airway epithelium and subepithelium with limited collagen deposition (arrow). (C) Nasal mucosa of the NP group exhibiting marked basement membrane thickening (arrows) and epithelial shedding. NP, nasal polyposis.

Figure 4

Distribution of total, infiltrating and activated eosinophils in the NP and control nasal mucosa specimens. Representative micrographs of (A) ICAM-1 and (B) ECP immunohistochemistry (brown stain) in NP specimens (magnification, ×200), revealing a large number of ICAM-1⁺ and ECP⁺ cells (arrows). (C) A representative micrograph of hematoxylin and eosin-stained NP specimens depicting marked eosinophil infiltration (arrows) of the nasal mucosa (magnification, ×200). Representative micrographs of negative control for (D) ICAM-1 and (E) ECP immunohistochemistry (magnification, ×400). (F) Distribution of total, ECP⁺ and ICAM-1⁺ eosinophils in NP and control groups. NP specimens exhibited higher cell counts for total eosinophils (P=0.030), ECP⁺ cells (P=0.006) and ICAM-1⁺ cells (P=0.007) than did control specimens. NP, nasal polyposis; ECP, eosinophil cationic protein; ICAM-1, intercellular adhesion molecule-1.