Basic and clinical immunology
Eosinophilic apoptosis in sinus mucosa: Relationship to tissue eosinophilia and its resolution in allergic sinusitis,☆☆

https://doi.org/10.1067/mai.2000.108909Get rights and content

Abstract

Background: Apoptosis, which is regulated by both cell survival and death signals, is important for the swift clearance of unwanted cells. Objective: We sought to elucidate whether eosinophilic apoptosis is associated with tissue eosinophilia and to determine its resolution in allergic sinusitis (AS). Methods: Numbers of eosinophils, numbers of IL-5+ cells, and the apoptosis index of eosinophils were calculated in the submucosa (both superficial and deep layers) of patients with AS by using histochemical methods before and after prednisolone treatment. Patients without AS were used for control groups. Anti-EG2 antibody was used to identify eosinophils. IL-5, Fas, or Bax expression of eosinophils was evaluated to elucidate the role of the factors affecting eosinophilic apoptosis. Results: EG2 and IL-5+ cells were abundant in the submucosa of patients with AS, especially in the superficial layer. About 50% to 60% of the IL-5–producing cells were eosinophils. Apoptotic eosinophils were less numerous in the superficial layer than the deep layer in these diseases. After prednisolone treatment, an induction of eosinophilic apoptosis was accompanied by a significant decrease in the number of EG2+ and IL-5+ cells. No remarkable difference was observed in the Fas or Bax expression of eosinophils after prednisolone treatment. Conclusion: Autocrine secretion of IL-5 from eosinophils may be one reason why eosinophilic disease is difficult to manage. Induction of eosinophilic apoptosis is critical for reversing tissue eosinophilia in patients with AS. (J Allergy Clin Immunol 2000;106:551-8.)

Section snippets

Patients and tissue samples

The 29 patients involved in this study ranged in age from 17 to 69 years. There were 19 men and 10 women. All patients had ethmoid and maxillary sinusitis and had undergone routine diagnostic procedures at the Department of Otolaryngology, Osaka Medical College. Specific IgE for 9 allergens (house dust mites, the major 5 Japanese pollens, dogs, cats, and fungus) was measured by using the CAP-RAST test in all patients. The diagnosis of AS was confirmed by the elevation of total serum IgE and

Eosinophil accumulation in AS

To assess eosinophil accumulation, anti-EG2 antibodies, which recognizes eosinophils in tissue, were used (Fig 1).

. EG2+ cells accumulated in the mucosa of patients with AS, especially in the superficial layer (magnification 250×).

This anti-EG2 antibody bound specifically to eosinophil cationic protein secreted (or extracted) from eosinophils. Results are shown in Table I.

. Eosinophil EG2+ cells per HPF

DiseaseSuperficial, mean ± SD (median)Deep, mean ± SD (median)P value*
AS (n = 13)114 ± 58 (102)

Discussion

In this study we revealed that EG2+ cells were abundant in allergic mucosa and dominated the superficial area, pointing to eosinophils as the main effector mediating inflammation in allergic tissue. To explore whether this accumulation was associated with eosinophilic apoptosis, we examined the eosinophil AI in superficial and deep layers of the mucosa. The low AI in the superficial layer was consistent with the theory that inhibition of apoptosis contributes to eosinophil accumulation.10, 11

Acknowledgements

We thank the staff of the Department of Otolaryngology, Osaka Medical College, for excellent assistance with this work.

References (34)

  • C Haslett

    Resolution of acute inflammation and the role of apoptosis in the tissue fate of granulocytes

    Clin Sci

    (1992)
  • GM Walsh

    Mechanism of human eosinophil survival and apoptosis

    Clin Exp Allergy

    (1997)
  • M Stern et al.

    Human monocyte-derived macrophage phagocytosis of senescent eosinophils undergoing apoptosis

    Am J Pathol

    (1996)
  • H-U Simon et al.

    Direct demonstration of delayed eosinophil apoptosis as a mechanism causing tissue eosinophilia

    J Immunol

    (1997)
  • H-U Simon et al.

    Inhibition of programmed eosinophil death: a key pathogenic event for eosinophilia?

    Immunol Today

    (1995)
  • T Miyashita et al.

    Tumor suppressor p53 is a direct transcriptional activator of the human Bax gene

    Cell

    (1995)
  • C Sugimoto et al.

    Apoptosis-promoting gene (bax) transfer potentiates sensitivity of squamous cell carcinoma to cisplatin in vitro and in vivo

    Int J Cancer

    (1999)
  • Cited by (19)

    • Twist1 sustains the apoptosis resistance in eosinophils in nasal mucosa of allergic rhinitis

      2021, Archives of Biochemistry and Biophysics
      Citation Excerpt :

      It has been recognized that the Eo accumulation in the local tissues plays a critical role in the pathogenesis of allergic diseases (e.g., AR, allergic asthma and allergic dermatitis) [1], but the underlying mechanism remains to be further investigated. Fan et al. suggest that the autocrine IL-5 production by Eos plays a critical role in the pathogenesis of allergic rhinosinusitis [20]. The present study provides mechanistic data to show the high Ras activation status in Eos isolated from AR nasal mucosal tissues.

    View all citing articles on Scopus

    Supported in part by grants-in-aid from the Society for Promotion of International Otorhinolaryngology, Japan.

    ☆☆

    Reprint requests: Hiroshi Takenaka, MD, Department of Otorhinolaryngology, Osaka Medical College, Daigaku-cho 2-7, Takatsuki, Osaka 0569-8686, Japan.

    View full text