The effects of β‐adrenoceptor stimulation on adhesion of human natural killer cells to cultured endothelium

Abstract

1 The circulation of natural killer (NK) 3 Cells were pretreated (15 min) with a selective P2-adrenoceptor antagonist, GR81706, at various concentrations. The duration of P-adrenoceptor blockade was tested by determining the adenosine 3',5'-cyclic monophosphate (cyclic AMP) production induced by terbutaline (a P2-adrenoceptor specific agonist). This receptor-mediated response was effectively inhibited for at least 4 h, whereas the cyclic AMP production in response to forskolin (a direct activator of adenylate-cyclase) was not affected. 4 Functional adhesion assays were then performed to determine the role of P-adrenoceptors on the different cell types involved (NK and EC) in catecholamine-induced detachment. Peripheral blood mononuclear cells were allowed to adhere for 1 h to monolayers of unstimulated EC in the presence or absence of cyclic AMP inducing agents, and the percentage of NK cells in the adhering lymphocyte fraction was determined by flow cytometry. 5 Both adrenaline (10-5 M) and forskolin (10-5 M) caused detachment of NK cells from EC. After blockade of the P2-adrenoceptors on NK cells by pretreatment with GR81706 (10-6 M), the effect of adrenaline on NK cells adhesion was pretented; after blockade of the P2-adrenoceptors on EC, NK cell adhesion was still significantly reduced by adrenaline. In all cases, forskolin caused detachment of NK cells.6 To establish further that stimulation of P-adrenoceptors on NK cells is sufficient to cause detachment, we showed that adrenaline also reduced adhesion of NK cells to monolayers of Chinese hamster ovary cells, which do not express P-adrenoceptors. 7 Together, these results show that stimulation of P2-adrenoceptors on NK cells negatively influences their capacity to adhere to EC, and that P2-adrenoceptors on EC play a negligible role in this phenomenon.

Impaired immune response to voluntary arm-crank ergometer exercise in patients with cervical spinal cord injury

“…16 The addition of a selective b-2 adrenoreceptor antagonist is reported to block this catecholamine-dependent detachment of NK cells. 17 Compared with noradrenaline, adrenaline was more effective in inducing detachment of the NK cells, which correlates with the higher affinity of b-2 adrenoreceptors for adrenaline. 4 A more recent report has emphasized that exercise-induced catecholamines modulate the expression of adhesion molecules on NK cells, resulting in the mobilization of NK cells into the circulation.…”

Selective Mobilization of Cytotoxic Leukocytes by Epinephrine

“…Earlier studies using this assay revealed distinctly reduced cell adhesion of NK or T cell populations after administration of b2-adrenoceptor agonists (2,41). Using the long-acting b2-adrenoceptor antagonist, GR81706, it was shown that this phenomenon is mediated via receptors on the leukocyte itself and not on the endothelium (62). Our in vitro experiments indicate that cytotoxic effector leukocytes display the highest adherence to activated endothelium, strongly suggesting that these cell populations form the predominant part of cells in the marginal pool also in the in vivo condition.…”

“…In summary, cytotoxic effector cell populations show a high expression of b2-adrenoceptors, CD11a and CX3CR1 that correspond to a great capability of these cells to be mobilized by epinephrine. A number of experiments indicates that b2-adrenoceptor-mediated leukocytosis is associated with an increase in intracellular cAMP (3,38,41,62,63). This second messenger was shown to attenuate chemokine triggered integrin affinity within seconds (60,61).…”

Comparative phytochemical analysis andin vivoimmunomodulatory activity of various extracts ofStevia rebaudianaleaves in experimental animal model

“…In this study, adherence to nylon fibres increased in the ethanolic and aqueous extracts of S. rebaudiana immunized group. This may be due to the upregulation of β 2 integrins and decreased corticosterone levels (Benschop et al 1994). Increased glucocorticoids level may also lead to this decrease in the neutrophil adherence (Benschop et al 1994).…”

“…This may be due to the upregulation of β 2 integrins and decreased corticosterone levels (Benschop et al 1994). Increased glucocorticoids level may also lead to this decrease in the neutrophil adherence (Benschop et al 1994). Phagocytosis by neutrophils is an essential part of host defence against foreign antigens.…”