Mast cells in neuroimmune function: Neurotoxicological and neuropharmacological perspectives

Abstract

Mast cells are located in close proximity to neurons in the peripheral and central nervous systems, suggesting a functional role in normal and aberrant neurodegenerative states. They also possess many of the features of neurons, in terms of monoaminergic systems, responsiveness to neurotrophins and neuropeptides and the ability to synthesise and release bioactive neurotrophic factors. Mast cells are able to secrete an array of potent mediators which may orchestrate neuroinflammation and affect the integrity of the blood-brain barrier. The 'cross-talk' between mast cells, lymphocytes, neurons and glia constitutes a neuroimmune axis which is implicated in a range of neurodegenerative diseases with an inflammatory and/or autoimmune component, such as multiple sclerosis and Alzheimer's disease. Mast cells appear to make an important contribution to developing, mature and degenerating nervous systems and this should now be recognised when assessing the neurotoxic potential of xenobiotics.

The expanding role of nerve growth factor: from neurotrophic activity to immunologic diseases

“…They are also resident within the normal nervous system, and are often observed in close apposition to neurons in various peripheral tissues (103,105). MC are associated classically with the hypersensitivity reactions involving the interaction of allergens and cell-fixed IgE (104,106). Although their role in anaphylaxis has been largely elucidated, research on these enigmatic cells has recently gained great interest after the observation that MC respond functionally (via specific receptors) to an enormous range of neuroactive compounds, including NGF, derived from both the central and peripheral nervous systems (18,20,75,107).…”

“…Considerable evidence published by many investigators indicates that MC and their endogenous products are strongly implicated not only in the classical immune processes, but also in neurophysiologic and neuropathologic events. MC are implicated in inflammatory and/or autoimmune diseases, such as multiple sclerosis, through the release of biologically active compounds, including NGF (105,106,108).…”

Distribution and local differentiation of mast cells in the parenchyma of the forebrain

“…Cultured mast cells can be activated by neurotransmitters, neuropeptides, neurotrophic factors, and steroid hormones (Theoharides, 1990;Theoharides et al, 1993;White, 1993;Horigome et al, 1993;Purcell and Atterwill, 1995). Mast cell/neuron co-cultures have demonstrated mast cell-nerve interaction with consequent physiologic effects on both mast cells and nerves (Janiszewski et al, 1990;Blennerhassett et al, 1992).…”

“…This privileged status is not absolute. Two populations of cells of the hematopoietic lineage are resident within the normal adult brain: mast cells (Johnson and Krenger, 1992;Purcell and Atterwill, 1995;Silver et al, 1996) and microglia (Williams and Hickey, 1995). The microglia enter the CNS as a precursor population (monocytes) and complete their differentiation within the CNS.…”

Untitled

“…In case of nerves somatic and autonomic are associated with inflammatory cells especially true of mast cells which resemble in different aspects 75,76 . Stimulation of sensory nerves containing C fibers with an electrical current, mechanically by heat or by noxious chemicals such as formalin or mustard oil or even loss ligation of the sciatic nerve 76,77 and resulting in antidromic transmission and ensures inflammatory response which is demonstrated in the eye, dental pulp, joints, lungs 76,78,79,80 .…”