According to the neurotrophic theory, the nerve growth factor (NGF) is widely distributed in the effector tissues of peripheral sympathetic and sensory neurons, suggesting that the density of innervation is controlled by effector derived NGF. Sympathetic neurons require access to NGF for survival throughout life, whereas sensory neurons are dependent on NGF only during restricted period of embryonic development. This development-related feature of sympathetic neurons suggests that they crucially depend on plasticity of NGF biology, including secretion, availability, and utilization, to maintain appropriate neuronal function in adult life, and even in old age. While most previous studies on the cellular source of NGF have focused on neuronal and nonneuronal effector cells, it was recently demonstrated that NGF secretion is not only restricted to cells receiving a direct innervation. Immune cells, including mast cells (MC), lymphocytes and macrophages, for example, produce and release NGF as well as NGF secretion-inducing cytokines. Likewise, since the first evidence that NGF treatment causes a significant increase in the number and size of MC has been published by Aloe and Levi-Montalcini in 1977, it has been repeatedly shown that these cells are also NGF-responsive cells, thus providing further evidence for a widely investigated MC-nerve interaction. Further on this trophobiological line, a positive correlation of the amount of NGF and expression of NGF mRNA with the density of sympathetic innervation was demonstrated in a variety of organs. In the rat heart, one such example, the atrium contains a higher amount of NGF corresponding to a denser sympathetic nerve supply compared to the ventricle. Such a correlation was also revealed in the submandibular glands (SMG) and iris. Likewise, the density of MC in the ankle joint capsule, which is heavily innervated, is greater than in the capsule of the knee, which is less densely innervated, and the MC number in the synovial joint of spontaneously hypertensive rats, which have increased sympathetic nerve supply, is significantly greater than in normotensive rats. A summing-up of the above mentioned data shows that (i) MC are NGF secreting/responsive cells and frequently colocalized with nerves, and (ii) a higher NGF amount correlates with a denser sympathetic innervation of a tissue . This, in our eyes, brings into question the sole contribution of the "classical" effector cells to neurotrophic support of sympathetic nerve-innervated tissues. Consequently, we suggest that MC, through their own and/or cytokine-induced NGF secretion, may also be implicated in the neurotrophic potential in these tissues.
Biomedical Reviews 1998; 9: 143-145.
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