Dental Pulp Inflammation Initiates the Occurrence of Mast Cells Expressing the α(1) and β(1) Subunits of Soluble Guanylyl Cyclase

The binding of nitric oxide (NO) to heme in the β(1) subunit of soluble guanylyl cyclase (sGC) activates both the heterodimeric α(1)β(1) and α(2)β(1) isoforms of the enzyme, leading to the increased production of cGMP from GTP. In cultured human mast cells, exogenous NO is able to inhibit mast cell degranulation via NO-cGMP signaling. However, under inflammatory oxidative or nitrosative stress, sGC becomes insensitive to NO. The occurrence of mast cells in healthy and inflamed human tissues and the in vivo expression of the α(1) and β(1) subunits of sGC in human mast cells during inflammation remain largely unresolved and were investigated here. Using peroxidase and double immunohistochemical incubations, no mast cells were found in healthy dental pulp, whereas the inflammation of dental pulp initiated the occurrence of several mast cells expressing the α(1) and β(1) subunits of sGC. Since inflammation-induced oxidative and nitrosative stress oxidizes Fe(2+) to Fe(3+) in the β(1) subunit of sGC, leading to the desensitization of sGC to NO, we hypothesize that the NO- and heme-independent pharmacological activation of sGC in mast cells may be considered as a regulatory strategy for mast cell functions in inflamed human dental pulp.