Lymph nodes—A possible site for sympathetic neuronal regulation of immune responses

Abstract

Noradrenergic fibers were identified in rat cervical lymph nodes by fluorescence histochemistry and confirmed by radioenzymatic determination of norepinephrine. After superior cervical ganglionectomy, lymph node norepinephrine and noradrenergic fluorescence were strikingly decreased. The alpha-adrenergic radioligand [3H] dihydroergocryptine bound to saturable sites on lymph node membranes (0.20 pmol/mg protein; affinity constant, 8 nM) with characteristics expected for alpha-adrenergic receptor binding. The alpha-adrenergic binding sites were present in high concentration in membranes from lymph node stroma but were negligible in membranes of lymphocytes teased from nodes. In lymph nodes the ratio of alpha-adrenergic binding sites to norepinephrine content was higher than ratios of many other sympathetically innervated tissues such as iris or vas deferens. The presence of sympathetic innervation and the high concentration of alpha-adrenergic binding sites relative to that innervation suggest that the sympathetic nervous system modulates an intrinsic lymph node function through alpha-adrenergic mechanisms.

Surgical Denervation of Ocular Sympathetic Afferents Decreases Local Transforming Growth Factor-β and Abolishes Immune Privilege

“…38 -41 Aside from supplying ocular structures, the sympathetic nerves that originate in the SCG also supply lymph nodes thought to process intraocular antigens including the cervical and submandibular lymph nodes. 42,43 In agreement with our results, prior studies have identified alterations in immune responsiveness within these lymph nodes as a result of SCGX. They include enhanced contact hypersensitivity, DTH, and graft versus host reactions.…”

Sympathetic modulation of immunity: Relevance to disease

“…The distribution of sympathetic nerves has been described in the lymph nodes from rats [7,100,[109][110][111][112][113], several strains of mice [5,110,111,113,114], cats, pigs and humans [110]; however, the origin of the NA nerves in lymph nodes is still unclear. It is presumed that their innervation is regionally supplied as lymph nodes are regional structures draining the areas with which they are associated.…”

“…It is presumed that their innervation is regionally supplied as lymph nodes are regional structures draining the areas with which they are associated. For example, in the rat when the superior cervical ganglia are removed, sympathetic nerves are lost in the cervical nodes [109]. NA nerves supplying the cervical, mesenteric and popliteal lymph nodes course along the vasculature that provides their blood supply [5,7,100,[109][110][111][112][113][114].…”

Nerve‐mediated contractions of sheep mesenteric lymph node capsules.

“…Morphological studies indicate that lymph nodes are innervated by a variety of fibre types including adrenergic (Giron, Crucher & Davis, 1980;Felten, Livnat, Felten, Carlsen, Bellinger & Yeh, 1984), substance P-containing and calcitonin generelated peptide-containing (Popper, Mantyh, Vigna, Maggio & Mantyh, 1988) types. It has been suggested that these nerves might modulate the immune system since sympathetic denervation of lymph nodes or the spleen alters the immune responsiveness of these organs (Besedovsky, Del Rey, Sorkin, Da Prada & Keller, 1979;Felten et al 1984;Popper et al 1988).…”