P-selectin enhances generation of CD14+ CD16+ dendritic-like cells and inhibits macrophage maturation from human peripheral blood monocytes

Geling Li, Young June Kim, Charlie Mantel, Hal Broxmeyer

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Endothelial cells play a critical role in monocyte differentiation. Platelets also affect terminal maturation of monocytes in vitro. P-selectin is an important adhesion molecule expressed on both endothelial cells and activated platelets. We investigated its effects on human peripheral blood monocyte differentiation under the influence of different cytokines. Generation of dendritic-like cells (DLCs) from peripheral blood monocytes was promoted by immobilized P-selectin in the presence of M-CSF and IL-4 as judged by dendritic cell (DC) morphology; increased expression of CD1a, a DC marker; low phagocytic activity; and high alloreactivity to naive T cells. In contrast to typical DCs, DLCs expressed CD14 and FcγRIII (CD16). These features link the possible identity of DLCs to that of an uncommon CD14+CD16+CD64- monocyte subset found to be expanded in a variety of pathological conditions. Functionally, DLCs generated by P-selectin in combination with M-CSF plus IL-4 primed naive allogeneic CD4+ T cells to produce significantly less IFN-γ than cells generated by BSA in the presence of M-CSF and IL-4. P-selectin effects on enhancing CD14+CD16+ DLC generation were completely abrogated by pretreatment of cells with the protein kinase C δ inhibitor rottlerin, but not by classical protein kinase C inhibitor Gö6976. Immobilized P-selectin also inhibited macrophage differentiation in response to M-CSF alone as demonstrated by morphology, phenotype, and phagocytosis analysis. The effects of P-selectin on macrophage differentiation were neutralized by pretreatment of monocytes with Ab against P-selectin glycoprotein ligand 1. These results suggest a novel role for P-selectin in regulating monocyte fate determination.

Original languageEnglish
Pages (from-to)669-677
Number of pages9
JournalJournal of Immunology
Volume171
Issue number2
StatePublished - Jul 15 2003

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P-Selectin
Dendritic Cells
Monocytes
Macrophages
Macrophage Colony-Stimulating Factor
Interleukin-4
Protein C Inhibitor
Protein Kinase Inhibitors
Protein Kinase C
Blood Platelets
Endothelial Cells
T-Lymphocytes
Phagocytosis
Cytokines
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

P-selectin enhances generation of CD14+ CD16+ dendritic-like cells and inhibits macrophage maturation from human peripheral blood monocytes. / Li, Geling; Kim, Young June; Mantel, Charlie; Broxmeyer, Hal.

In: Journal of Immunology, Vol. 171, No. 2, 15.07.2003, p. 669-677.

Research output: Contribution to journalArticle

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