Moran Elishmereni

Physical interactions between mast cells and eosinophils: a novel mechanism enhancing eosinophil survival in vitro

To cite this article: Elishmereni M, Alenius HT, Bradding P, Mizrahi S, Shikotra A, Minai‐Fleminger Y, Mankuta D, Eliashar R, Zabucchi G, Levi‐Schaffer F. Physical interactions between mast cells and eosinophils: a novel mechanism enhancing eosinophil survival in vitro. Allergy 2011; 66: 376–385.

Physical interactions between mast cells and eosinophils: a novel mechanism enhancing eosinophil survival in vitro.

To cite this article: Elishmereni M, Alenius HT, Bradding P, Mizrahi S, Shikotra A, Minai‐Fleminger Y, Mankuta D, Eliashar R, Zabucchi G, Levi‐Schaffer F. Physical interactions between mast cells and eosinophils: a novel mechanism enhancing eosinophil survival in vitro. Allergy 2011; 66: 376–385.

CD48: A co-stimulatory receptor of immunity.

The CD48 molecule is a glycosyl-phosphatidyl-inositol (GPI)-anchored cell-surface protein of the CD2 family of molecules. Originally described on virally-induced B cells, CD48 has been found on various hematopoietic cells, and its expression is regulated by viral and bacterial products and immune-associated proteins. CD48 binds CD2 and other molecules, yet its high-affinity ligand in both mouse and human systems is 2B4. Despite its lack of an intracellular domain, stimulation of CD48 induces rearrangement of signaling factors in lipid rafts, Lck-kinase activity, and tyrosine phosphorylation. As an adhesion and co-stimulatory molecule, CD48 induces numerous effects in B and T lymphocytes, natural killer cells, mast cells, and eosinophils. Some of these depend upon cell-cell interactions via 2B4-CD48 binding. The structural and phenotypic characteristics of CD48, and its role in physiological and pathophysiological processes, are reviewed herein. Possible CD48-based applications for immune-impaired and inflammatory disorders are discussed as well.

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 others 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.

Complex 2B4 Regulation of Mast Cells and Eosinophils in Murine Allergic Inflammation

The cell surface molecule 2B4 (CD244) is an important regulator of lymphocyte activation, and its role in antiviral immunity and lymphoproliferative disorders is well established. Although it is also expressed on mast cells (MCs) and eosinophils (Eos), the functions of 2B4 on these allergy-orchestrating cells remain unclear. We therefore investigated the role of 2B4 on murine MCs and Eos, particularly how this molecule affects allergic and nonallergic inflammatory processes involving these effector cells. Experiments in bone marrow-derived cultures revealed an inhibitory effect for 2B4 in MC degranulation, but also an opposing stimulatory effect in eosinophil migration and delayed activation. Murine disease models supported the dual 2B4 function: In 2B4-/- mice with nonallergic peritonitis and mild atopic dermatitis (AD), modest infiltrates of Eos into the peritoneum and skin (respectively) confirmed that 2B4 boosts eosinophil trafficking. In a chronic AD model, 2B4-/- mice showed overdegranulated MCs, confirming the inhibiting 2B4 effect on MC activation. This multifunctional 2B4 profile unfolded in inflammation resembles a similar mixed effect of 2B4 in natural killer cells. Taken together, our findings provide evidence for physiological 2B4 stimulatory/inhibitory effects in MCs and Eos, pointing to a complex role for 2B4 in allergy.

Skin Disorders of Inflammation and Immune Suppression in Young and Elder: A Special Role for Mast Cells

Publisher Summary This chapter presents up-to-date epidemiology and pathogenesis of skin diseases that are linked with immune alterations and age. It reviews the current knowledge regarding skin immunity in general, and mast cell function in particular. In addition, the manner by which deterioration of these immune mechanisms promotes both skin aging and skin disease progression has been examined. One of the most acute problems in the elderly is the high incidence of skin diseases. Most cutaneous pathologies classified with high prevalence, morbidity, and mortality, are age-dependent. Likewise, the majority of these skin diseases is immune-related, presenting in individuals, whose skin immunity is no longer intact. Management of these skin disorders, namely parasitic infections, allergic inflammation, and cancer, therefore necessitates the targeting of factors at the core of the malfunctioning immune system. In the case of cancer and infectious diseases, current treatments target the hazardous element and/or intensify the immune response against it. Conventional treatment approaches, both in cancer and in inflammation, yield significant toxicity and high variation in patient response, thereby limiting drug dosing and disease control. Newer avenues are therefore being developed. By means of hindering activatory signaling or stimulating inhibitory signaling, mast cells can theoretically be driven to stability and senescence, affording long lasting abrogation of disease pathogenesis.