Sulfated glycosphingolipid as mediator of phagocytosis: SM4s enhances apoptotic cell clearance and modulates macrophage activity.
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-beta1, 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.
Popovic
Zoran V
ZV
Department of Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Germany. Z.Popovic@dkfz.de
Sandhoff
Roger
R
Sijmonsma
Tjeerd P
TP
Kaden
Sylvia
S
Jennemann
Richard
R
Kiss
Eva
E
Tone
Edgar
E
Autschbach
Frank
F
Platt
Nick
N
Malle
Ernst
E
Gröne
Hermann-Josef
HJ
D000418:Albumins / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D006017:Glycolipids / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000096:biosynthesis; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D015846:Monokines / Q000096:biosynthesis; D019007:P-Selectin / Q000096:biosynthesis; D011379:Prognosis; D051116:Receptors, Scavenger / Q000819:agonists / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis
D000418:Albumins; D014408:Biomarkers, Tumor; D006017:Glycolipids; C508600:IL6 protein, human; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D015846:Monokines; D019007:P-Selectin; D051116:Receptors, Scavenger; D053773:Transforming Growth Factor beta1; C099252:oxidized low density lipoprotein; C011117:sulfoglycolipids