Autonomes Nervensystem und Immunabwehr: Bedeutung der noradrenergen Innervation für die Migration von Splenozyten in die Milz

Naive as well as memory T-lymphocytes migrate continuously from the blood into lymphatic and non-lymphatic tissues. They reach secondary immunorgans via blood- and lymphatic vessels, but the spleen is only reached via blood vessels. Here cell uptake depends on the regulation of splenic perfusion. The spleen's role is emphasized by the amount of immigrated cells that equals the amount of immigrated cells to all lymphatic tissues which are drained by the thoracic duct. This work investigates two aspects of cell immigration into the spleen: on the one hand the influence of the innervation and resulting perfusion, and on the other hand the influence of bacterial endotoxin (e. coli's LPS) and the following immune stimulation. The majority of noradrenergic fibers addresses the smooth muscles of vessels ( 60-80%), a minority (20-30%) reaches T-lymphocytes in the white pulpa. This reflects the importance of blood circulation for the cell migration. Lymphocyte stimulation, Interleukin-1 production and expression of adhesionmolecules are endotoxin effects. Hence, local molecular mechanisms are at work here. WKY-rats were used for measuring the uptake of fluorescent labeled splenocytes from the blood into the spleen over a period of 24 hours at maximum. The main results are: 1. LPS-stimulation of the recipient 6 hours prior to cell injection results in a significantly higher uptake of leukocytes by the spleen. 2. Local denervation through surgically cutting the splenic nerve leads to a significantly higher immigration of cells to the spleen, the amount equals the uptake after immune stimulation. 3. General sympathectomy with Reserpin shows a significantly reduced migration to the spleen even in comparison with the controls 4. Splenic perfusion is 2.5 times higher after LPS-stimulation and local denervation than at rest, the perfusion of other parenchymatous organs and the heart minute volume are unchanged. Perfusion of parenchamtous organs is increased after general sympathectomy, the percentage of the heart minute volume going to the spleen remains unchanged. 5. These results imply that increased local perfusion and the following increased amount of cells offered support the cell immigration into the spleen. General vasodilatation leads to a re-distribution of blood perfusion to other parenchymatous organs and, therefore, a reduced uptake of cells to the spleen. These results show that apart from molecular mechanisms hemodynamic factors influence the regulation of leukocyte immigration to the spleen. 6. The influence of adhesionsmolecules and chemokines on cellmigration is not questioned, but the influence of the autonomic regulation of blood flow for the general conditions under which molecular mechanisms can take effect are stressed in this work.