P-glycoprotein functions as a differentiation switch in antigen presenting cell maturation.

P-glycoprotein functions as a differentiation switch in antigen presenting cell maturation. Research Abstract Details 

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P-glycoprotein functions as a differentiation switch in antigen presenting cell maturation. Abstract Text:

S S Pendse,S Behjati,T Schatton,A Izawa,M H Sayegh,M H Frank,

P-glycoprotein (P-gp) expressed on human antigen presenting cells (APC) regulates alloantigen-dependent T-cell activation, but the associated mechanisms are not well understood. Here we demonstrate that P-gp functions in IL-12-dependent monocyte differentiation into dendritic cell (DC) lineages during APC maturation, thereby regulating the capacity of myeloid-derived APCs to elicit alloimmune Th1 responses. Human CD14+ monocytes cultured in vitro in the presence of IL-4/GM-CSF differentiated into CD14(-) CD1A+ APCs of the immature DC phenotype. In contrast, P-gp blockade during differentiation inhibited CD1a induction, down-regulated CD80 expression, enhanced CD86 expression and induced CD68 expression. APCs differentiated in the presence of P-gp blockade stimulated alloimmune T-cell proliferation significantly less than controls and this effect was associated with 97% inhibition of Th1 IFN-gamma production, but preserved Th2 IL-5 secretion. MAb-mediated blockade of the P-gp transport substrate IL-12 in the course of APC differentiation also inhibited IFN-gamma production, while addition of rIL-12 to P-gp-blocked APC differentiation cultures significantly reversed this effect, demonstrating that P-gp functions in APC differentiation in part via IL-12 regulation. Our findings define a novel role for P-gp as a differentiation switch in APC maturation and resultant alloimmune Th1 responses, thereby identifying P-gp as a potential novel therapeutic target in allotransplantation.

P-glycoprotein functions as a differentiation switch in antigen presenting cell maturation. Publishing Authors By Initials

SS Pendse,S Behjati,T Schatton,A Izawa,MH Sayegh,MH Frank,

For similar cells: blood cells: leukocytes: leukocytes, mononuclear: lymphocytes: t-lymphocytes research abstracts see: cells: blood cells: leukocytes: leukocytes, mononuclear: lymphocytes: t-lymphocytes research

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P-glycoprotein functions as a differentiation switch in antigen presenting cell maturation. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: American journal of transplantation : official jou

VOLUME: 6

Page Numbers: 2884-93

Journal Abbreviation: Am. J. Transplant.

ISSN: 1600-6135

DAY: 3

MONTH: Dec

YEAR: 2006

P-glycoprotein functions as a differentiation switch in antigen presenting cell maturation. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100968638

P-glycoprotein functions as a differentiation switch in antigen presenting cell maturation. Keywords Mesh Terms:

KEYWORDS: T-Lymphocytes

MESH TERMS: immunology

Chemical & Substance for Abstract: P-glycoprotein functions as a differentiation switch in antigen presenting cell maturation. Information

Substance Name: Granulocyte-Macrophage Colony-Stimulatin

Registry Number: 83869-56-1

Grant and Affiliation Information for P-glycoprotein functions as a differentiation switch in antigen presenting cell maturation.

AFFILIATION: Transplantation Research Center, Children's Hospital Boston, Massachusetts, USA.

Country: Denmark

AGENCY: United States NIAID

GRANT: K08 AI50783

ACRONYM: AI

MEDLINETA: Am J Transplant

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