In vitro and in vivo Regulation of Non-specific Immune Responses in Carp (Cyprinus carpio L.)

Beschreibung

Innate immunity is critical in self-defense for the host against microbial infections, in which macrophages play central roles in the initiation of inflammation by producing proinflammatory cytokines and bactericidal radical effector molecules. Especially, the inducible nitric oxide synthase (iNOS) plays a central role in the inflammatory reactions that follow infection or tissue damage. The production of antimicrobial NO performs both beneficial and detrimental actions. It is thus conceivable that regulatory mechanisms exist which control the timing and intensity of NO production by iNOS. Intracellular concentrations of calcium and the cyclic nucleotides cAMP and cGMP regulate a multitude of physiological processes. To measure cellular responses to changes of these secondary messengers in carp leukocytes treatments were performed using primary cell cultures derived from head and trunk kidneys of carps. It was observed that increases in calcium conductance may be important in signaling these cells to undergo apoptosis. The present study also provided evidence that a negative feedback between intracellular cGMP levels and NO production is present in carp leukocytes. Furthermore, the secondary messenger cAMP produced by adenylyl cyclases (ACs) plays a key role in the regulation of many cellular functions. The obtained data provide evidence that the AC/cAMP signaling pathway is well established in carp leukocytes and leads to antiinflammatory immune responses. The effects of stress on fishes, especially on their immune system, have been of recent concern. The increase of stress hormones (glucocorticoids) in fish is known to mainly induce antiinflammatory reactions. Accordingly, NO production was shown to be impaired by glucocorticoids in carp leukocytes derived from head and trunk kidneys in vitro and in vivo. In contrast to mammals, the involvement of sexual steroids in direct and indirect regulation and modulation of immune responses is not well recognized in fish. In in vitro studies direct effects on progestogens on NO signaling were investigated to increase the knowledge about immunomodulatory effects of progestogens using also synthetic compounds. The findings demonstrated for the first time that progestogens are involved in immune signaling cascades in fish. Moreover, an important locus of action of these hormones appears to be at the transcription level. Furthermore, it was demonstrated that progestogens are capable of influencing the innate immunity in fish in in vivo experiments as well. The induction of regulatory type II immune responses by progestogens is a striking example of interference of female steroid-mediated events with the piscine immune system. Thus, the present data provide initial information on influence of the testing compounds on the immune function of carp leukocytes.

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Constanze Pietsch

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arginine metabolism fish immune system progestogens secondary messengers

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