Pollen grains, as one of the most common inducers of type I allergy, are thought to induce allergy in susceptible individuals by the release of a specific protein. However, the epithelium of the upper respiratory tract- being the primary site of exposure to pollen grains - is not only exposed to the protein but to the whole pollen grain. It has been recently demonstrated that pollen grains not only function as allergen carriers but are also a rich source of bioactive lipid mediators stimulating and attracting cells of the innate immune system. In this study we show that soluble factors from pollen also stimulate the adaptive immune system in terms of phenotypical and functional maturation of monocyte derived dendritic cells. Chemokine production in immature and mature dendritic cells was also analyzed in the presence or absence of aqueous pollen extracts (Bet.-APE) from birch. Exposure to Bet.-APE induced upregulation of MHC class II, CD83, CD86 and increased allostimulatory activity. However, Bet.-APE -promoted DC maturation led to a low IL-12 production in comparison to CD40L or LPS. Furthermore, costimulation of Bet.-APE and LPS showed that Bet.-APE blocked LPS induced IL12 production while IL-6, IL-10 and TNF-α release remained unchanged. Consequently, the ensuing T-cell response of naïve T-cells stimulated by Bet.-APE -matured DC resulted in a Th2 subtype. As one causative substance in Bet.-APE for this effect, phytoprostane E1 was identified to antagonize the LPS- induced IL-12 production. We also examined the effects of Bet.-APE on chemokinereceptor expression and chemokine production by DCs. Bet.-APE strongly induced expression of CXC chemokine receptor 4 on both immature and lipopolysaccharide (LPS)-stimulated DCs. In contrast, Bet.-APE reduced CCR5 and CCR1 expression on immature DCs. These effects were confirmed at both messenger RNA and protein levels. Furthermore, Bet.-APE significantly reduced LPS-induced production of interferoninducible protein 10 (CXCL10) and regulated upon activation, normal T-cell expressed and secreted chemokine (CCL5); increased secretion of macrophage-derived chemokine (CCL22) and did not change production of thymus and activation-regulated chemokine (CCL17). Consistent with these findings, supernatants from Bet.-APE- treated mature DCs attracted Th1 type T cells less efficiently whereas migration of Th2 type T cells was enhanced. Our data suggest that Bet.-APE provide a signal for enhanced lymph node localization of DCs, but that it may, at the same time, diminish the capacity of DCs to amplify type 1 immune response increasing the outcome and amplification of a Th2 type immune response.     «

Pollen grains, as one of the most common inducers of type I allergy, are thought to induce allergy in susceptible individuals by the release of a specific protein. However, the epithelium of the upper respiratory tract- being the primary site of exposure to pollen grains - is not only exposed to the protein but to the whole pollen grain. It has been recently demonstrated that pollen grains not only function as allergen carriers but are also a rich source of bioactive lipid mediators stimulating...     »

Pollen sind als Allergenträger und somit als Allergie-auslösende Substanzen klar identifiziert. Pollen setzen jedoch nicht nur Allergene sondern auch bioaktive Lipidmediatoren frei. Neben proinflammatorischen PALMs konnten wir in Pollenextrakten eine weitere Gruppe von Lipidmediatoren mit immunmodulierender Wirkung identifizieren. Diese bestand in einer Verminderung der LPS-induzierten Freisetzung von IL-12, dem Schlüsselzytokin in der Ausbildung von Typ1 T-Helferantworten (Th1). Mit Hilfe chemischer Analysen (GC-MS) konnte Phytoprostan E1 als die bioaktive Substanz – Hemmung der LPS-induzierten IL-12-Produktion – in wässrigen Pollenextrakten identifiziert werden. Darüber hinaus führen PALMs in humanen dendritischen Zellen zu einer vermehrten chemotaktischen Aktivierung von Th2 im Vergleich zu Th1-Zellen. Es ist anzunehmen, dass die Freisetzung von immunmodulierenden PALMs am Ort der Pollenexposition die Funktion dendritischer Zellen derart beeinflusst, dass bevorzugt Allergie-fördernde Th2-Immunantworten auf die gleichzeitig freigesetzten Pollenallergene gebildet werden.     «

Pollen sind als Allergenträger und somit als Allergie-auslösende Substanzen klar identifiziert. Pollen setzen jedoch nicht nur Allergene sondern auch bioaktive Lipidmediatoren frei. Neben proinflammatorischen PALMs konnten wir in Pollenextrakten eine weitere Gruppe von Lipidmediatoren mit immunmodulierender Wirkung identifizieren. Diese bestand in einer Verminderung der LPS-induzierten Freisetzung von IL-12, dem Schlüsselzytokin in der Ausbildung von Typ1 T-Helferantworten (Th1). Mit Hilfe chemi...     »