CD48 Expression on Eosinophils in Nasal Polyps of Chronic Rhinosinusitis Patients.

INTRODUCTION: The pathogenesis of chronic rhinosinusitis (CRS) with nasal polyps (CRSwNPs) is not yet completely understood. Based on current knowledge, the infiltration of mast cells and eosinophils in nasal polyps (NPs) plays an important role. This study aimed to investigate the interplay of asthma and allergy etiopathology in CRSwNPs patients by specifically studying tissue mast cells and eosinophils and the pro-inflammatory marker CD48. METHODS: Immunohistochemistry was used to assess eosinophils, mast cells, and CD48 expressing eosinophils infiltrating NPs, and flow cytometry was used to assess surface receptors expression on eosinophils from digested NPs. RESULTS: Immunohistochemical analyses showed that mast cell infiltration in NPs is higher in allergic patients in comparison to nonallergic patients; eosinophils infiltration in asthmatic NPs was significantly elevated in comparison to the nonasthmatic NPs, and membrane CD48 (mCD48) expression on eosinophils infiltrating nonallergic asthmatic NPs was highly elevated in comparison to the other subgroups. Similarly, mCD48 and its high-affinity ligand m2B4's expression on eosinophils from enzymatically digested NPs were significantly higher in nonallergic asthmatics in comparison to allergic asthmatics. CONCLUSIONS: Eosinophil infiltration in NPs for asthmatic patients, and mast cell infiltration for allergic patients, may be used as reliable biomarkers for endotyping CRSwNPs. In addition, CD48 in asthmatic patients who developed CRSwNPs could be regarded as a potential target for treatment.

Ultrastructural evidence for human mast cell-eosinophil interactions in vitro.

We have hypothesized that mast cells (MC) and eosinophils (Eos), the main effectors of allergy, can form an effector unit. These cells co-exist in the inflamed tissues during the late and chronic stages of allergy and have been shown to be capable of influencing each other's survival and activity via soluble mediators. We have recently described couples of receptor-ligands that are expressed on either/both of these cells and that imply a physical interaction. In this study, we have investigated the existence of short-term (60 min) in vitro interactions between human peripheral blood Eos and cord-blood-derived MC by transmission electron microscopy. We have found that MC and Eos adhere to each other; the lipid body content and the granule morphology of co-cultured MC and Eos, respectively, are altered, and the level of Eos peroxidase (EPO) released by co-cultured Eos is elevated. Moreover, the transfer of EPO from Eos to MC and tryptase from MC to Eos has been observed. Our results thus indicate that, when co-cultured, MC and Eos show signs of physical contact and of reciprocal activation. This is the first in vitro evidence of functional physical interactions between human MC and Eos, interactions that might also occur in vivo during allergic diseases.

Mast cells and eosinophils: the two key effector cells in allergic inflammation.

The allergic inflammatory response is composed of two main phases--the early and the late. The early phase initiates when an allergen activates the tissue resident mast cell, triggering the release of a variety of granule-stored and newly formed mediators. As the inflammatory response progresses, blood borne inflammatory cells--in particular, eosinophils--are recruited into the inflamed tissue. Eosinophil activation and consequent release and production of several pro-inflammatory mediators results in the late phase reaction. A chronic allergic inflammation always features prominent tissue eosinophilia. In this review, we will discuss the possible channels of communication, both soluble and physical, between mast cells and eosinophils that can occur in the late and chronic stages of allergy. Such interactions, that we have termed "the allergic effector unit", may modulate the severity and/or duration of the allergic inflammatory reaction.