Dual mode of catecholamine action on splenic macrophage phagocytosis in wall lizard, Hemidactylus flaviviridis

In the present study, in vitro con centration-related effect of catecholamines, dopamine (DA), norepinephrine (NE), and epinephrine (E) was observed on phagocytic activity of splenic macrophages to understand the impact of sympatho-adrenal-medullary (SAM) activation on innate immunity in wall lizard Hemidactylus flaviviridis under stress condition. Restraint stress for 1 h resulted in marked suppression of macrophage phagocytosis, suggesting that supra-physiological level of catecholamines in response to SAM activation under stress suppressed phagocytosis. This interpretation was reinforced since all the catecholamines considerably reduced phagocytosis at high concentrations ranging from 10(-7) to 10(-5) M. On the contrary, DA, NE, and E at low concentrations considerably stimulated phagocytosis, which increased with the decrease of concentrations ranging from 10(-11) to 10(-15) M. Further, effect of NE and E was blocked by beta-adrenergic blocker suggesting the beta-adrenoceptor-dependent regulating mechanism of NE and E. DA acts through both beta-adrenoceptor-dependent and D1/D2 class receptor-dependent mechanism, since beta-adrenergic blocker could partially block the DA effect. beta-Adrenoceptor-linked adenylate cyclase-mediated cAMP action in modulation of phagocytic activity was evident as 3-isobutyl-1-methyl-xanthine suppressed phagocytosis. Further, to delineate the mode of dual effect of catecholamines through beta-adrenergic receptors, in vitro concentration-related effect of cAMP was investigated on macrophage phagocytosis. cAMP depending on concentration had opposite effect on phagocytosis, and its stimulatory effect at low concentrations was reversed by actinomycin D and cycloheximide, whereas these transcription and translation inhibitors, respectively, failed to alter the inhibitory effect of cAMP at high concentrations. This suggests the concentration-related two different pathways of catecholamine action, classical non-genomic at high concentration while genomic pathway at low concentration. (C) 2004 Elsevier Inc. All rights reserved.