Involvement of substance P, mast cells, TNF-α and ICAM-1 in the infiltration of inflammatory cells in human periapical granulomas

Background: Substance P (SP), a potent proinflammatory peptide present in sensory neurons, is believed to be a major mediator of neurogenic inflammation. The aim of this study was to examine the localization and involvement of SP, mast cells and tumor necrosis factor-α (TNF-α)-positive cells in human periapical granulomas. Methods: Sections from seven periapical granulomas were stained using a variety of immunohistochemical methods. Results: SP-immunoreactive nerve fibers, mast cells and TNF-α-positive cells were found localized in the vicinity of blood vessels in all the samples of periapical granulomas. The vascular endothelial cells stained positively for E-selectin and intercellular adhesion molecule-1. SP, TNF-α-positive cells and E-selectin could not be detected in clinically healthy periodontal ligament, and served as a negative control. Conclusion: Our findings suggest that SP, mast cells, TNF-α-positive cells and E-selectin may modulate the pathogenesis of apical periodontitis and may be responsible for stimulating the formation of granuloma with the resorption of periapical bone.