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Enzyme
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Gene/Protein
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Target Concepts:
Gene/Protein
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Query: UNIPROT:P06126 (
CD1a
)
2,221
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Platelet factor 4
(
PF4
) is a CXC chemokine secreted by activated platelets.
PF4
has been shown to promote monocyte survival and induce the differentiation of monocytes into macrophages. However, the effect of
PF4
on differentiation of monocytes into dendritic cells (DC) has yet to be determined. As reported previously, monocytes cultured in RPMI medium containing FCS, granulocyte macrophage colony stimulating factor and IL-4 differentiated into CD1a+ DC. When
PF4
was added, the expression of
CD1a
on DC was inhibited. This inhibitory effect was not observed with the other platelet-derived CXC chemokine, beta-thromboglobulin. The relative number of
CD1a
- DC increased from 17 to 92% when the
PF4
concentration was increased from 0 to 10 micro g/ml. The inhibitory effect of
PF4
on
CD1a
expression was reversed by 50 U/ml heparin. DC developed in the
PF4
-containing media appeared more adhesive to plastic culture wells and had higher light side scatter by flow cytometry. Immunophenotypically, monocyte-derived DC in the presence of increasing concentrations of
PF4
proportionally expressed higher CD86 and lower HLA-DR. The levels of CD11c, CD40 and CD80 remained unchanged with or without
PF4
. Both CD1a+ DC and
CD1a
- DC were negative for CD14, CD68 and CD83. Functionally, DC developed in the presence of
PF4
had their secretion of tumor necrosis factor-alpha and IL-12 reduced by 75 +/- 10 and 79 +/- 13% respectively when they were stimulated by 100 ng/ml lipopolysaccharide and 50 ng/ml IFN-gamma.
CD1a
- DC developed in the presence of
PF4
were not as active as the control CD1a+ DC in stimulating allogeneic T cells to proliferate. In addition,
CD1a
- DC were less potent in priming naive CD4+ T cells to secrete both type 1 and 2 cytokines. These results indicate that
PF4
can influence differentiation and function of monocyte-derived DC.
...
PMID:Effect of CXC chemokine platelet factor 4 on differentiation and function of monocyte-derived dendritic cells. 1288 38
Upon inflammation, circulating monocytes leave the bloodstream and migrate into the tissues, where they differentiate after exposure to various growth factors, cytokines or infectious agents. The best defined macrophage polarization types are M1 and M2. However, the platelet-derived CXC chemokine
CXCL4
induces the polarization of macrophages into a unique phenotype. In this study, we compared the effect of
CXCL4
and its variant CXCL4L1 on the differentiation of monocytes into macrophages and into immature monocyte-derived dendritic cells (iMDDC). Differently to M-CSF and
CXCL4
, CXCL4L1 is not a survival factor for monocytes. Moreover, the expression of the chemokine receptors CCR2, CCR5 and CXCR3 was significantly higher on CXCL4L1-treated monocytes compared to M-CSF- and
CXCL4
-stimulated monocytes. IL-1 receptor antagonist (IL-1RN) expression was upregulated by
CXCL4
and downregulated by CXCL4L1, respectively, whereas both chemokines reduced the expression of the mannose receptor (MRC). Furthermore, through activation of CXCR3, CXCL4L1-stimulated monocytes released significantly higher amounts of CCL2 and CXCL8 compared to
CXCL4
-treated monocytes, indicating more pronounced inflammatory traits for CXCL4L1. In contrast, in CXCL4L1-treated monocytes, the production of CCL22 was lower. Compared to iMDDC generated in the presence of CXCL4L1,
CXCL4
-treated iMDDC showed an enhanced phagocytic capacity and downregulation of expression of certain surface markers (e.g.
CD1a
) and specific enzymes (e.g. MMP-9 and MMP-12).
CXCL4
and CXCL4L1 did not affect the chemokine receptor expression on iMDDC and cytokine production (CCL2, CCL18, CCL22, CXCL8, IL-10) by
CXCL4
- or CXCL4L1-differentiated iMDDC was similar. We can conclude that both
CXCL4
and CXCL4L1 exert a direct effect on monocytes and iMDDC. However, the resulting phenotypes are different, which suggests a unique role for the two
CXCL4
variants in physiology and/or pathology.
...
PMID:CXCL4 and CXCL4L1 Differentially Affect Monocyte Survival and Dendritic Cell Differentiation and Phagocytosis. 2782 99
