DECENTRALIZATION OF THE SUPERIOR CERVICAL-GANGLIA INHIBITS MAST-CELL MEDIATED TNF-ALPHA-DEPENDENT CYTOTOXICITY .1. POTENTIAL ROLE OF SALIVARY-GLANDS

Decentralization or ganglionectomy of the superior cervical ganglia (SCG) reduces pulmonary inflammation, as well as chemotaxis and activation of circulating neutrophils. However, the protective effect of decentralization was abolished when combined with removal of the submandibular glands (sialadenectomy) in the same animals. Thus, it has been postulated that the submandibular glands (SMG) release an anti-inflammatory factor(s) that is controlled by cervical sympathetic nerves. Decentralization of SCG did not modify in vitro histamine release or in vivo levels of rat mast cell protease II, but it reduced mast cell (MC)-mediated tumor necrosis factor α (TNFα)-dependent cytotoxicity. Combined decentralization/sialadenectomy abrogated the inhibition of MC cytotoxic activity, as we have shown previously for pulmonary inflammation and neutrophil functions. However, sialadenectomy alone inhibited MC-mediated TNFα-dependent cytotoxicity, an observation which suggests that SMG produce a factor(s) that can potentiate MC cytotoxic activity. Studies of the effects of SMG-derived factors, such as epidermal growth factor, nerve growth factor, and transforming growth factor β (TGF(β)), showed that only pretreatment of MCs with TGF(β) 10-8 g/ml inhibited MC-mediated TNFα-dependent cytotoxicity. Thus, the modulation of MC-mediated TNFα-dependent cytotoxicity by cervical sympathetic innervation and SMG is complex and distinct from the modulation of pulmonary inflammation and neutrophil functions identified previously. © 1993 Academic Press, Inc.