Rapid spread of mannan to the immune system, skin and joints within 6 hours after local exposure

Author:

Hagert C12ORCID,Siitonen R3,Li X-G34,Liljenbäck H35,Roivainen A356,Holmdahl R17

Affiliation:

1. Medical Inflammation Research, MediCity Research Laboratory, University of Turku, Turku, Finland

2. The National Doctoral Programme in Informational and Structural Biology, Turku, Finland

3. Turku PET Centre, University of Turku, Turku, Finland

4. Turku PET Centre, Åbo Akademi University, Turku, Finland

5. Turku Center for Disease Modeling, University of Turku, Turku, Finland

6. Turku PET Centre, Turku University Hospital, Turku, Finland

7. Medical Inflammation Research, Department of Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden

Abstract

Summary Psoriasis (Ps), psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are common diseases dependent on environmental factors that activate the immune system in unknown ways. Mannan is a group of polysaccharides common in the environment; they are potentially pathogenic, because at least some of them induce Ps-, PsA- and RA-like inflammation in mice. Here, we used positron emission tomography/computed tomography to examine in-vivo transport and spread of mannan labelled with fluorine-18 [18F]. The results showed that mannan was transported to joints (knee) and bone marrow (tibia) of mice within 6 h after intraperitoneal injection. The time it took to transport mannan, and its presence in blood, indicated cellular transport of mannan within the circulatory system. In addition, mannan was filtered mainly through the spleen and liver. [18F]fluoromannan was excreted via kidneys, small intestine and, to some extent, the mouth. In conclusion, mannan reaches joints rapidly after injection, which may explain why mannan-induced inflammatory disease is targeted to these tissues.

Funder

the Turku University Foundation

State Research Funding from Turku University Hospital

Sigrid Juséliuksen Säätiö

Suomen Kulttuurirahasto

Jane ja Aatos Erkon Säätiö

Vetenskapsrådet

the Swedish Foundation for Strategic Research

Knut och Alice Wallenbergs Stiftelse

the Drug Research Doctoral Programme of University of Turku Graduate School

the National Doctoral Programme in Informational and Structural Biology

Stiftelsen Konung Gustaf V:s 80-årsfond

Varsinais-Suomen Rahasto

Suomen Akatemia

Academy of Finland

Sigrid Jusélius Foundation

University of Turku

Finnish Cultural Foundation

Varsinais-Suomi Regional Fund

Swedish Foundation for Strategic Research

Swedish Research Council

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

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