SPARC (secreted protein acidic and rich in cysteine) of the intestinal nematode Strongyloides ratti is involved in mucosa-associated parasite-host interaction.
The secreted protein acidic and rich in cysteine (SPARC), found in the excretory/secretory products of Strongyloides ratti, is most strongly expressed in parasitic females. Since SPARC proteins are involved in the modulation of cell-matrix interactions, a role of the secreted S. ratti SPARC (Sr-SPARC) in the manifestation of the parasite in the host's intestine is postulated. The full-length cDNA of Sr-SPARC was identified and the protein was recombinantly expressed. The purified protein was biologically active, able to bind calcium, and to attach to mucosa-associated human cells. Addition of Sr-SPARC to an in vitro mucosal three-dimensional-cell culture model led to a time-dependent release of the cytokines TNF-α, IL-22, IL-10 and TSLP. Of importance, exposure with Sr-SPARC fostered wound closure in an intestinal epithelial cell model. Here, we demonstrate for the first time that SPARC released from the nematode is a multifunctional protein affecting the mucosal immune system.
Department of Molecular Physiology, Westfälische Wilhelms-University Münster, Schlossplatz 8, D-48143 Münster, Germany; Department Molecular Medicine, Bernhard-Nocht-Institute, Bernhard-Nocht-Strasse 74, 20259 Hamburg, Germany.
Emmanuela M
EM
Anandarajah
Department of Molecular Physiology, Westfälische Wilhelms-University Münster, Schlossplatz 8, D-48143 Münster, Germany; Department Molecular Medicine, Bernhard-Nocht-Institute, Bernhard-Nocht-Strasse 74, 20259 Hamburg, Germany.
Dana
D
Ditgen
Department Tissue Engineering and Regenerative Medicine (TERM) and Fraunhofer IGB, University Würzburg, Germany.
Jan
J
Hansmann
Department Molecular Medicine, Bernhard-Nocht-Institute, Bernhard-Nocht-Strasse 74, 20259 Hamburg, Germany.
Klaus D
KD
Erttmann
Department of Molecular Physiology, Westfälische Wilhelms-University Münster, Schlossplatz 8, D-48143 Münster, Germany.
Eva
E
Liebau
Department Molecular Medicine, Bernhard-Nocht-Institute, Bernhard-Nocht-Strasse 74, 20259 Hamburg, Germany. Electronic address: nbrattig@bni-hamburg.de.
Norbert W
NW
Brattig
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D015801:Helminth Proteins / Q000737:chemistry / Q000378:metabolism*; D006790:Host-Parasite Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D015676:Osteonectin / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017170:Strongyloides ratti / Q000502:physiology*; D013322:Strongyloidiasis / Q000276:immunology* / Q000469:parasitology; D014945:Wound Healing
D016207:Cytokines; D015801:Helminth Proteins; D015676:Osteonectin; D011994:Recombinant Proteins; D002118:Calcium
3D- cell culture; Excretory/secretory products; Immune response; SPARC; Strongyloides