Bidirectional Mast Cell–Eosinophil Interactions in Inflammatory Disorders and Cancer

Abstract

Human mast cells (MCs) and eosinophils were first described and named by Paul Ehrlich. These cells have distinct myeloid progenitors and differ morphologically, ultrastructurally, immunologically, biochemically, and pharmacologically. However, MCs and eosinophils play a pivotal role in several allergic disorders. In addition, these cells are involved in autoimmune disorders, cardiovascular diseases, and cancer. MCs are distributed throughout all normal human tissues, whereas eosinophils are present only in gastrointestinal tract, secondary lymphoid tissues, and adipose tissue, thymus, mammary gland, and uterus. However, in allergic disorders, MCs and eosinophils can form the “allergic effector unit.” Moreover, in several tumors, MCs and eosinophils can be found in close proximity. Therefore, it is likely that MCs have the capacity to modulate eosinophil functions and vice versa. For example, interleukin 5, stem cell factor, histamine, platelet-activating factor (PAF), prostaglandin D2 (PGD2), cysteinyl leukotrienes, and vascular endothelial growth factors (VEGFs), produced by activated MCs, can modulate eosinophil functions through the engagement of specific receptors. In contrast, eosinophil cationic proteins such as eosinophil cationic protein and major basic protein (MBP), nerve growth factor, and VEGFs released by activated eosinophils can modulate MC functions. These bidirectional interactions between MCs and eosinophils might be relevant not only in allergic diseases but also in several inflammatory and neoplastic disorders.

Duodenal low‐grade inflammation and expression of tight junction proteins in functional dyspepsia

“…There were correlations in the number of infiltrated eosinophils and mast cells in the duodenum of patients with FD in this study. Accumulated data indicated that eosinophils and mast cells can affect each other's viability, functionality, trafficking, and activation . Although factors from these cells and the direct interaction of mast cells and eosinophils were not assessed in this study, in vitro studies indicated that the physical interaction between mast cells and eosinophils induces a hyperactive state and release of soluble mediators .…”

Human eosinophils and mast cells: Birds of a feather flock together

“…The fact that omalizumab can effectively reduce exacerbations further supports the role of MCs in late‐phase responses (reviewed in ). Moreover, MC‐derived substances contribute to the recruitment of other immune cells such as lymphocytes, macrophages, and eosinophils . The release of mediators such as histamine, PGD 2 , LTC 4 , cytokines and others by MCs contribute to bronchoconstriction, mucus secretion, and mucosal edema .…”

“…Eosinophils on the other hand can release GM‐CSF, IL‐2, IL‐10, IL‐12, IL‐13, RANTES (CCL5), and eotaxin (CCL11) among others upon their activation by Th2 cytokines such as IL‐5 . Notably, some mediators are produced by both MCs and eosinophils, such as SCF, IL‐4, IL‐5, IL‐6, and TNFα, although quantities released per cell vary and can often be quite small . The evidence that MCs and eosinophils release some common cytokines and chemokines points out their shared capacity to influence similar pathophysiological processes and even each other via paracrine mechanisms.…”

“…181 Notably, some mediators are produced by both MCs and eosinophils, such as SCF, IL-4, IL-5, IL-6, and TNFα, although quantities released per cell vary and can often be quite small. [188][189][190] The evidence that MCs and eosinophils release some common cytokines and chemokines points out their shared capacity to influence similar pathophysiological processes and even each other via paracrine mechanisms. MCs store and release preformed TNFα.…”

“…226 Moreover, MC-derived substances contribute to the recruitment of other immune cells such as lymphocytes, macrophages, and eosinophils. 190 The release of mediators such as histamine, PGD 2 , LTC 4 , cytokines and others by MCs contribute to bronchoconstriction, mucus secretion, and mucosal edema. 232 The role of eosinophils in asthma, via release of granule proteins and other substances, is probably multifactorial (reviewed by 198).…”