Nerve‐mast cell interaction in normal guinea pig urinary bladder

Abstract

Urinary bladders of normal adult female guinea pigs were analyzed for anatomical evidence of nerve-mast cell interaction using light microscopy and electron microscopy. Nerves, ganglia, and individual nerve fibers were visualized on paraffin sections using immunohistochemistry with antisera against the neural antigens neurofilament protein and protein gene product 9.5, and sections were also immunoreacted with antisera against the neuropeptides substance P and calcitonin gene-related peptide. Separate mast cell populations were identified by counterstaining with toluidine blue and alcian blue. Mast cells of both types were found within nerves and intramural ganglia and were in close contact with individual nerve fibers displaying substance P- and calcitonin gene-related peptide-like immunoreactivity. Moreover, serotonin-immunoreactive mast cells were innervated with nerve fibers that reacted with antiserum against vasoactive intestinal polypeptide. At the ultrastructural level, these fibers were almost exclusively identified as unmyelinated primary sensory afferents. Mast cells contacted these fibers with lamellipodia that wrapped around and enclosed the fibers deeply within the cell. Close association between mast cells, nerves, and vessels was common. Ultrastructural evidence suggests that bidirectional communication occurs between nerve fibers and mast cells. These structures may participate in axon reflexes that regulate normal vascular and detrusor smooth muscle function and cause vasodilation, edema, inflammation, and bladder hyperreactivity. In summary, a close relationship exists between mast cells and peptidergic nerve fibers, including primary sensory afferents. Results suggest that bidirectional interaction could occur between nerves and mast cells.

Lack of neurokinin-1 receptor expression affects tissue mast cell numbers but not their spatial relationship with nerves

“…We also showed that mast cells in the bladder are frequently in direct contact with nerve elements (22), and there was functionality associated with this connection (9,10).…”

“…In these tissues and other sites, mast cells have close anatomic proximity to lymphatics (56), vascular endothelial cells (21), and nerve elements (22), but the factors that potentially influence mast cell interactions with other cells are not completely understood.…”

“…This pattern of distribution facilitates the exposure of mast cells to stimuli, such as soluble protein, antigens (26), or neuropeptides (10), that can induce activation. Furthermore, it places the mast cell at the interface of potentially critical host-pathogen interactions (6, 28) and in turn makes their cell products available to a variety of cell types in the microenvironment, including sensory and autonomic nerves (22,47,48) and smooth muscle cells (16 -18).…”

“…In this context, nerve-mast cell interaction has been described in the skin and in the gastrointestinal (GI) and urinary tracts (4, 30, 33, 50). Early studies elegantly described the nonrandom spatial association of mast cells with nerves in a variety of tissues in which actual membrane-membrane contacts occur (11,22,32,44,47,48). In the GI tract, several studies have suggested that mast cell-nerve interaction has an important homeostatic role in the regulation of gut physiology as well pathophysiology (57).…”

C-kit receptor in the human vas deferens: distinction of mast cells, interstitial cells and interepithelial cells

“…There is clear evidence that MC may also contribute to smooth muscle activity and neural stimulation by releasing a variety of substances (Keith et al 1995, Corvera et al 1999, Hollenberg & Bunnett 1999, Reed et al 2003, Vodenicharov et al 2005. Histamines, prostaglandins and leukotrienes are potential paracrine signals in the communication pathways between MC and intrinsic (Zarate et al 2006).…”