Central nervous system neurons acquire mast cell products via transgranulation

Abstract

Resting and actively degranulating mast cells are found on the brain side of the blood-brain barrier. In the periphery, exocytosis of mast cell granules results in the release of soluble mediators and insoluble granule remnants. These mast cell constituents are found in a variety of nearby cell types, acquired by fusion of granule and cellular membranes or by cellular capture of mast cell granule remnants. These phenomena have not been studied in the brain. In the current work, light and electron microscopic studies of the medial habenula of the dove brain revealed that mast cell-derived material can enter neurons in three ways: by direct fusion of the granule and plasma membranes (mast cell and neuron); by capture of insoluble granule remnants and, potentially, via receptor-mediated endocytosis of gonadotropin-releasing hormone, a soluble mediator derived from the mast cell. These processes result in differential subcellular localization of mast cell material in neurons, including free in the neuronal cytoplasm, membrane-bound in granule-like compartments or in association with small vesicles and the trans-Golgi network. Capture of granule remnants is the most frequently observed form of neuronal acquisition of mast cell products and correlates quantitatively with mast cells undergoing piecemeal degranulation. The present study indicates that mast cell-derived products can enter neurons, a process termed transgranulation, indicating a novel form of brain-immune system communication.

Mast cells: an expanding pathophysiological role from allergy to other disorders

“…These include adhesion molecules expressed over mast cells and neurons such as cell adhesion molecule-1 (CADM) (Ito et al 2003) and N-cadherin (Suzuki et al 2004) along with transgranulation (neuronal uptake of intragranular mast cell particles) and exosome transfer (Wilhelm et al 2005).…”

The role of the immune system in central nervous system plasticity after acute injury

“…Growthpromoting molecules secreted by innate immune cells stimulate the intrinsic growth machinery of neurons to overcome surrounding inhibitory environment (Silver and Miller, 2004). MCs attach to growing neurites (Furuno et al, 2005) where they can synthesize, store and release NGF, thus enhancing axonal sprouting of neuronal networks (Wilhelm et al, 2005). Similarly, eosinophils synthesize specific neurotrophins, including NGF, brainderived neurotrophic factor (BDNF) and neurotrophin (NT)-3, that can be released upon stimulation (Kobayashi et al, 2002) and have major stimulatory effect on neurite outgrowth (Foster et al, 2011).…”

Alteraciones Histopatológicas de los Bulbos Olfatorios de Cachama Blanca ante una Presentación Comercial de Glifosato: (Roundup® Activo)

“…Por otro lado, según los reportado por Wilhelm et al 2005, en mamíferos las células mast (homologas de las CG) pueden interactuar con las neuronas por procesos de transgranulación, ya sea por fusión directa de los gránulos y las membranas plasmáticas de ambas células, por la captura de restos de gránu-los insolubles tras los eventos de degranulación de las células mast o por endocitosis de estas.…”