HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Data Supplement Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Popovic, Z. V. Articles by Gröne, H.-J. Search for Related Content PubMed PubMed Citation Articles by Popovic, Z. V. Articles by Gröne, H.-J.

Sulfated Glycosphingolipid as Mediator of Phagocytosis: SM4s Enhances Apoptotic Cell Clearance and Modulates Macrophage Activity¹

Zoran V. Popovic^2,*, Roger Sandhoff^*, Tjeerd P. Sijmonsma^*, Sylvia Kaden^*, Richard Jennemann^*, Eva Kiss^*, Edgar Tone^*, Frank Autschbach, Nick Platt, Ernst Malle and Hermann-Josef Gröne^2,*

^* Department of Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Germany; Institute of Pathology, School of Medicine, Ruprecht-Karls University of Heidelberg, Heidelberg, Germany; School of Biological Sciences, University of Southampton, Southampton, United Kingdom; and Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria

Sulfoglycolipids are present on the surface of a variety of cells. The sulfatide SM4s is increased in lung, renal, and colon cancer and is associated with an adverse prognosis, possibly due to a low immunoreactivity of the tumor. As macrophages significantly contribute to the inflammatory infiltrate in malignancies, we postulated that SM4s may modulate macrophage function. We have investigated the effect of SM4s on the uptake of apoptotic tumor cells, macrophage cytokine profile, and receptor expression. Using flow cytometry and microscopic analyses, we found that coating apoptotic murine carcinoma cells from the colon and kidney with SM4s promoted their phagocytosis by murine macrophages up to 3-fold ex vivo and in vivo. This increased capacity was specifically inhibited by preincubation of macrophages with oxidized or acetylated low density lipoprotein and maleylated albumin, indicating involvement of scavenger receptors in this interaction. The uptake of SM4s-coated apoptotic cells significantly enhanced macrophage production of TGF-β1, expression of P-selectin, and secretion of IL-6. These data suggest that SM4s within tumors may promote apoptotic cell removal and alter the phenotype of tumor-associated macrophages.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a Deutsche Forschungsgemeinschaft Grant Gr 728-6 and SFB 405, B10 (to H.-J.G.) and Fonds zur Förderung der Wissenschaftlichen Forschung Grant P19074-B05 (to E.M.).

² Address correspondence and reprint requests to Dr. Hermann-Josef Gröne and Dr. Zoran V. Popovic, Department of Cellular and Molecular Pathology, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, Germany. E-mail addresses: H.-J.Groene{at}dkfz.de and Z.Popovic{at}dkfz.de

³ Abbreviations used in this paper: GSL, glycosphingolipid; PS, phosphatidylserine; SR, scavenger receptors; PSR, phosphatidylserine receptor; PI, propidium iodide; IHC, immunohistochemistry; TLC, thin-layer chromatography; nLDL, native low density lipoprotein; OxLDL, copper low density lipoprotein; AcLDL, sodium acetate/acetic anhydride low density lipoprotein; MBSA, Maleyl-BSA; TAM, tumor-associated macrophages.

⁴ The online version of this article contains supplemental material.