The Journal of Experimental Medicine
ThymUS '08
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Published 22 February 2005. doi:10.1084/jem.20041065
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 4, 627-636
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ARTICLE

 Pollen-associated phytoprostanes inhibit dendritic cell interleukin-12 production and augment T helper type 2 cell polarization

Claudia Traidl-Hoffmann1, Valentina Mariani1, Hubertus Hochrein2, Kathrin Karg4, Hermann Wagner2, Johannes Ring3, Martin J. Mueller4, Thilo Jakob1,3, and Heidrun Behrendt1

1 ZAUM-Center for Allergy and Environment, Division of Environmental Dermatology and Allergy GSF/TUM
2 Institute of Medical Microbiology, Immunology and Hygiene
3 Department of Dermatology and Allergy Biederstein, Technische, Universität München, 80802 Munich, Germany
4 Julius-von-Sachs-Institute of Biosciences, Division of Pharmaceutical Biology, University of Würzburg, 97082 Würzburg, Germany

CORRESPONDENCE Thilo Jakob: thilo.jakob{at}gsf.de

Pollen grains induce allergies in susceptible individuals by release of allergens upon contact with mucosal membranes of the upper respiratory tract. We recently demonstrated that pollen not only function as allergen carriers but also as rich sources of bioactive lipids that attract cells involved in allergic inflammation such as neutrophils and eosinophils. Here we demonstrate that soluble factors from birch (Betula alba L.) pollen activate human dendritic cells (DCs) as documented by phenotypical and functional maturation and altered cytokine production. Betula alba L. aqueous pollen extracts (Bet.-APE) selectively inhibited interleukin (IL)-12 p70 production of lipopolysaccharide (LPS)- or CD40L-activated DC, whereas IL-6, IL-10, and TNF{alpha} remained unchanged. Presence of Bet.-APE during DC activation resulted in DC with increased T helper type 2 (Th2) cell and reduced Th1 cell polarizing capacity. Chemical analysis of Bet.-APE revealed the presence of phytoprostanes (dinor isoprostanes) with prostaglandin E1-, F1-, A1-, or B1-ring systems of which only E1-phytoprostanes dose dependently inhibited the LPS-induced IL-12 p70 release and augmented the Th2 cell polarizing capacity of DC. These results suggest that pollen-derived E1-phytoprostanes not only resemble endogenous prostaglandin E2 structurally but also functionally in that they act as regulators that modulate human DC function in a fashion that favors Th2 cell polarization.

Abbreviations used: Bet.-APE, Betula alba L. aqueous pollen extracts; LAL, Limulus amebocyte lysate; NCI GC-MS, negative chemical ionization gas chromatography-mass spectrometry; PALM, pollen-associated lipid mediator; PP, phytoprostanes.

C. Traidl-Hoffmann and T. Jakob contributed equally to this work.


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