Untersuchung möglicher Effekte von HAV sowie von Immunglobulin A auf die Bildung und Funktion von myeloiden und lymphatischen Zellen

Abstract

A transient suppression of hematopoiesis can be observed frequently during an HAV infection. HAV inhibits the monocyte to macrophage differentiation in vitro. Because the bone marrow macrophages contribute to the maintenance of a balanced hematopoiesis, this might be the reason for the impaired hematopoiesis. For further investigations it has been tried to adapt the virus to monocytic cell lines. However, with none of the used virus variants, the various inoculation schedules and cell lines an infection of monocytes could be obtained. This suggests that the virus does not result in infection of monocytes in vivo and possibly binding of the virus to the cells is sufficient to interfere with their function. As it was previously described that the incubation of monocytes with HAV triggers an upregulation of Siglec-7 and -9, the expression pattern of these inhibitory molecules was investigated as a possible alternative mechanism for the inhibition of monocyte to macrophage differentiation. However this effect could neither observed for the cell lines nor for primary peripheral monocytes. It has also been studied whether IgA acts as a transport molecule for antigenic substances to the thymus and contributes to selection processes and the formation of T-cells in this organ. By such a mechanism allergies against harmless foreign antigens might be prevented. It was investigated to which extent the complexation of various substances (HAV, Salmonella enteritidis and molecules linked to a MRT contrast agent) with IgA influenced the distribution pattern in mice, the transport to the thymus or to the tissue surrounding the thymus. After i.p injection IgA/HAV complexes were enriched in the tissue surrounding the thymus but not in the thymus. For Salmonella, however, the opposite effect was observed regarding the tissue surrounding the thymus. No antigens could be detected in the thymus itself. The use of molecules coupled to contrast agents showed no specific accumulation of substances or immune complexes in any organ (apart from the bladder). Therefore, the hypothesis could not be supported or disproved with the achieved results. Thus, the use of other antigens or other specific IgA antibodies and sophisticated methods are essential to clarify the question.