Numerous studies have shown that stress, bereavement, and psychosocial factors can influence the function of the immune system. One of the key components of the stress response is the release of catecholamines from the adrenal medulla and from sympathetic nerve terminals. Thus, lymphocytes which are exposed to catecholamines in the blood and in the innervated T cell compartments of the lymphoid tissues have altered responses as a result of stress or in vivo catecholamine stimulation. This gives rise to the possibility that the immune potential of patients with diseases such as Acquired Immune Deficiency Syndrome (AIDS) can be modulated by catecholamine interactions with their T cells. Since lymphocytes are mobile cells, such alterations could be the result of a change in the trafficking pattern of resting and activated lymphocytes leading to a change in the population of lymphocytes in the lymphoid tissues, as has been suggested by several studies that demonstrate modulatory effects of stress and catecholamines on the Migratory properties of lymphocytes. The studies in this proposal will investigate the effect of catecholamines on lymphocyte migration, particularly the interaction of lymphocytes with the specialized high endothelial cells in the lymphoid tissues that are the site of lymphocyte extravasation from the blood into these tissues. Ibis interaction is dependent on the binding of the adhesion molecules Mel- 14 and LFA- 1 on the lymphocytes to addressins and ICAM- 1, respectively, on the endothelial cells. Thus, the hypothesis is that exposure, of lymphocytes or endothelial cells to catecholamines will modulate the adhesion molecules expressed on these cells, resulting in a change in lymphocyte trafficking and distribution in the lymphoid tissues. Catecholamine modulation of lymphocyte trafficking will be investigated at three levels: 1) the in vivo trafficking patterns of catecholamine-stimulated or control lymphocytes will be examined histologically and by cell sorter analysis to determine if the distribution of the cells is altered; 2) the ability of catecholamines to modulate the affinity and expression of the adhesion molecules on resting and activated T cells and endothelial cells will be determined via assays of lymphocyte binding to endothelial cells and by FACS analysis of adhesion molecule expression; 3) the cellular and molecular mechanisms of catecholamine-mediated modulation of the T cell adhesion molecules will be examined. These results will aid in understanding the role of catecholamines in psychoneuroimmunology.
| Carlson, S L; Johnson, S; Parrish, M E et al. (1998) Development of immune hyperinnervation in NGF-transgenic mice. Exp Neurol 149:209-20 |
| Carlson, S L; Fox, S; Abell, K M (1997) Catecholamine modulation of lymphocyte homing to lymphoid tissues. Brain Behav Immun 11:307-20 |
| Carlson, S L; Beiting, D J; Kiani, C A et al. (1996) Catecholamines decrease lymphocyte adhesion to cytokine-activated endothelial cells. Brain Behav Immun 10:55-67 |
| Carlson, S L; Albers, K M; Beiting, D J et al. (1995) NGF modulates sympathetic innervation of lymphoid tissues. J Neurosci 15:5892-9 |
| Selliah, N; Bartik, M M; Carlson, S L et al. (1995) cAMP accumulation in T-cells inhibits anti-CD3 monoclonal antibody-induced actin polymerization. J Neuroimmunol 56:107-12 |
| Carlson, S L; Trauth, K; Brooks, W H et al. (1994) Enhancement of beta-adrenergic-induced cAMP accumulation in activated T-cells. J Cell Physiol 161:39-48 |
