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The CD16(+) (FcgammaRIII(+)) subset of human monocytes preferentially becomes migratory dendritic cells in a model tissue setting.

Randolph GJ, Sanchez-Schmitz G, Liebman RM, Schäkel K - J. Exp. Med. (2002)

Bottom Line: These DCs migrate across endothelium in the ablumenal-to-lumenal direction (reverse transmigration), reminiscent of the migration into lymphatic vessels.CD16 was not functionally required for reverse transmigration, but promoted cell survival when yeast particles (zymosan) were present as a maturation stimulus in the subendothelial matrix.We propose that CD16(+) monocytes may contribute significantly to precursors for DCs that transiently survey tissues and migrate to lymph nodes via afferent lymphatic vessels.

View Article: PubMed Central - PubMed

Affiliation: The Carl C. Icahn Institute for Gene Therapy and Molecular Medicine, Mt. Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA. gwendalyn.randolph@mssm.edu

ABSTRACT
Much remains to be learned about the physiologic events that promote monocytes to become lymph-homing dendritic cells (DCs). In a model of transendothelial trafficking, some monocytes become DCs in response to endogenous signals. These DCs migrate across endothelium in the ablumenal-to-lumenal direction (reverse transmigration), reminiscent of the migration into lymphatic vessels. Here we show that the subpopulation of monocytes that expresses CD16 (Fcgamma receptor III) is predisposed to become migratory DCs. The vast majority of cells derived from CD16(+) monocytes reverse transmigrated, and their presence was associated with migratory cells expressing high levels of CD86 and human histocompatibility leukocyte antigen (HLA)-DR, and robust capacity to induce allogeneic T cell proliferation. A minority of CD16(-) monocytes reverse transmigrated, and these cells stimulated T cell proliferation less efficiently. CD16 was not functionally required for reverse transmigration, but promoted cell survival when yeast particles (zymosan) were present as a maturation stimulus in the subendothelial matrix. The cell surface phenotype and migratory characteristics of CD16(+) monocytes were inducible in CD16(-) monocytes by preincubation with TGFbeta1. We propose that CD16(+) monocytes may contribute significantly to precursors for DCs that transiently survey tissues and migrate to lymph nodes via afferent lymphatic vessels.

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Effect of a reverse transmigration antagonist on the distribution of CD16+ cells in endothelial cell cultures. PBMCs were incubated with endothelial/collagen cultures for 1.5 h, then washed to remove nonadherent, nonmigrated cells. Cultures were fed with medium containing mAb to MDR-1 or isotype-matched control mAb UPC10, and incubation was continued for 48 h to allow reverse transmigration. The presence of CD16+ cells in reverse-transmigrated and subendothelial leukocytes was monitored after 48 h by flow cytometry. The total number of CD16+ cells recovered from cultures in the presence and absence of anti-MDR-1 is shown. The fraction of such cells that had reverse transmigrated (R/T) is shown by the open portion of the bars, whereas the fraction that remained in the subendothelium (S/E) is shown by the filled portion of the bars.
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fig4: Effect of a reverse transmigration antagonist on the distribution of CD16+ cells in endothelial cell cultures. PBMCs were incubated with endothelial/collagen cultures for 1.5 h, then washed to remove nonadherent, nonmigrated cells. Cultures were fed with medium containing mAb to MDR-1 or isotype-matched control mAb UPC10, and incubation was continued for 48 h to allow reverse transmigration. The presence of CD16+ cells in reverse-transmigrated and subendothelial leukocytes was monitored after 48 h by flow cytometry. The total number of CD16+ cells recovered from cultures in the presence and absence of anti-MDR-1 is shown. The fraction of such cells that had reverse transmigrated (R/T) is shown by the open portion of the bars, whereas the fraction that remained in the subendothelium (S/E) is shown by the filled portion of the bars.

Mentions: In contrast to the reverse-transmigrated cells recovered from unstimulated cultures, the vast majority of monocyte-derived cells remaining in the subendothelium were CD16− (Fig. 3) and M-DC8− (unpublished data). That CD16+ cells could be recovered from the subendothelial collagen after only 1.5 h of incubation (Fig. 2) argues that our failure to detect CD16 on the surface of monocyte-derived cells that remained in the subendothelium was not due to cleavage of the relevant CD16 epitope during recovery of these cells from the collagen using collagenase D. Furthermore, CD16+ cells were recovered from the subendothelial matrix after 48 h when we prevented reverse transmigration using an antagonist to the p-glycoprotein lipid transporter ABCB1 (10; Fig. 4) .


The CD16(+) (FcgammaRIII(+)) subset of human monocytes preferentially becomes migratory dendritic cells in a model tissue setting.

Randolph GJ, Sanchez-Schmitz G, Liebman RM, Schäkel K - J. Exp. Med. (2002)

Effect of a reverse transmigration antagonist on the distribution of CD16+ cells in endothelial cell cultures. PBMCs were incubated with endothelial/collagen cultures for 1.5 h, then washed to remove nonadherent, nonmigrated cells. Cultures were fed with medium containing mAb to MDR-1 or isotype-matched control mAb UPC10, and incubation was continued for 48 h to allow reverse transmigration. The presence of CD16+ cells in reverse-transmigrated and subendothelial leukocytes was monitored after 48 h by flow cytometry. The total number of CD16+ cells recovered from cultures in the presence and absence of anti-MDR-1 is shown. The fraction of such cells that had reverse transmigrated (R/T) is shown by the open portion of the bars, whereas the fraction that remained in the subendothelium (S/E) is shown by the filled portion of the bars.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196052&req=5

fig4: Effect of a reverse transmigration antagonist on the distribution of CD16+ cells in endothelial cell cultures. PBMCs were incubated with endothelial/collagen cultures for 1.5 h, then washed to remove nonadherent, nonmigrated cells. Cultures were fed with medium containing mAb to MDR-1 or isotype-matched control mAb UPC10, and incubation was continued for 48 h to allow reverse transmigration. The presence of CD16+ cells in reverse-transmigrated and subendothelial leukocytes was monitored after 48 h by flow cytometry. The total number of CD16+ cells recovered from cultures in the presence and absence of anti-MDR-1 is shown. The fraction of such cells that had reverse transmigrated (R/T) is shown by the open portion of the bars, whereas the fraction that remained in the subendothelium (S/E) is shown by the filled portion of the bars.
Mentions: In contrast to the reverse-transmigrated cells recovered from unstimulated cultures, the vast majority of monocyte-derived cells remaining in the subendothelium were CD16− (Fig. 3) and M-DC8− (unpublished data). That CD16+ cells could be recovered from the subendothelial collagen after only 1.5 h of incubation (Fig. 2) argues that our failure to detect CD16 on the surface of monocyte-derived cells that remained in the subendothelium was not due to cleavage of the relevant CD16 epitope during recovery of these cells from the collagen using collagenase D. Furthermore, CD16+ cells were recovered from the subendothelial matrix after 48 h when we prevented reverse transmigration using an antagonist to the p-glycoprotein lipid transporter ABCB1 (10; Fig. 4) .

Bottom Line: These DCs migrate across endothelium in the ablumenal-to-lumenal direction (reverse transmigration), reminiscent of the migration into lymphatic vessels.CD16 was not functionally required for reverse transmigration, but promoted cell survival when yeast particles (zymosan) were present as a maturation stimulus in the subendothelial matrix.We propose that CD16(+) monocytes may contribute significantly to precursors for DCs that transiently survey tissues and migrate to lymph nodes via afferent lymphatic vessels.

View Article: PubMed Central - PubMed

Affiliation: The Carl C. Icahn Institute for Gene Therapy and Molecular Medicine, Mt. Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA. gwendalyn.randolph@mssm.edu

ABSTRACT
Much remains to be learned about the physiologic events that promote monocytes to become lymph-homing dendritic cells (DCs). In a model of transendothelial trafficking, some monocytes become DCs in response to endogenous signals. These DCs migrate across endothelium in the ablumenal-to-lumenal direction (reverse transmigration), reminiscent of the migration into lymphatic vessels. Here we show that the subpopulation of monocytes that expresses CD16 (Fcgamma receptor III) is predisposed to become migratory DCs. The vast majority of cells derived from CD16(+) monocytes reverse transmigrated, and their presence was associated with migratory cells expressing high levels of CD86 and human histocompatibility leukocyte antigen (HLA)-DR, and robust capacity to induce allogeneic T cell proliferation. A minority of CD16(-) monocytes reverse transmigrated, and these cells stimulated T cell proliferation less efficiently. CD16 was not functionally required for reverse transmigration, but promoted cell survival when yeast particles (zymosan) were present as a maturation stimulus in the subendothelial matrix. The cell surface phenotype and migratory characteristics of CD16(+) monocytes were inducible in CD16(-) monocytes by preincubation with TGFbeta1. We propose that CD16(+) monocytes may contribute significantly to precursors for DCs that transiently survey tissues and migrate to lymph nodes via afferent lymphatic vessels.

Show MeSH
Related in: MedlinePlus