Innate Immun 2012,
PMID: 21088050
Schwartzkopff, Franziska; Petersen, Frank; Grimm, Tobias Alexander; Brandt, Ernst
During acute inflammation, monocytes are essential in abolishing invading micro-organisms and encouraging wound healing. Recruitment by CC chemokines is an important step in targeting monocytes to the inflamed tissue. However, cell surface expression of the corresponding chemokine receptors is subject to regulation by various endogenous stimuli which so far have not been comprehensively identified. We report that the platelet-derived CXC chemokine ligand 4 (CXCL4), a known activator of human monocytes, induces down-regulation of CC chemokine receptors (CCR) 1, -2, and -5, resulting in drastic impairment of monocyte chemotactic migration towards cognate CC chemokine ligands (CCL) for these receptors. Interestingly, CXCL4-mediated down-regulation of CCR1, CCR2 and CCR5 was strongly dependent on the chemokine's ability to stimulate autocrine/paracrine release of TNF-α. In turn, TNF-α induced the secretion CCL3 and CCL4, two chemokines selective for CCR1 and CCR5, while the secretion of CCR2-ligand CCL2 was TNF-α-independent. Culture supernatants of CXCL4-stimulated monocytes as well as chemokine-enriched preparations thereof reproduced CXCL4-induced CCR down-regulation. In conclusion, CXCL4 may act as a selective regulator of monocyte migration by stimulating the release of autocrine, receptor-desensitizing chemokine ligands. Our results stress a co-ordinating role for CXCL4 in the cross-talk between platelets and monocytes during early inflammation.
Diseases/Pathways annotated by Medline MESH: Inflammation
Document information provided by NCBI PubMed
Text Mining Data
chemokine receptors (CCR) 1 ⊣ chemokine ligand 4: "
We report that the platelet derived CXC
chemokine ligand 4 ( CXCL4 ), a known activator of human monocytes,
induces down-regulation of CC
chemokine receptors (CCR) 1 , -2, and -5, resulting in drastic impairment of monocyte chemotactic migration towards cognate CC chemokine ligands (CCL) for these receptors
"
chemokine receptors (CCR) 1 ⊣ CXCL4: "
We report that the platelet derived CXC chemokine ligand 4 ( CXCL4 ), a known activator of human monocytes, induces down-regulation of CC chemokine receptors (CCR) 1 , -2, and -5, resulting in drastic impairment of monocyte chemotactic migration towards cognate CC chemokine ligands (CCL) for these receptors
"
CCR1 ⊣ CXCL4: "
Interestingly, CXCL4 mediated down-regulation of CCR1 , CCR2 and CCR5 was strongly dependent on the chemokine 's ability to stimulate autocrine/paracrine release of TNF-a
"
CCR2 ⊣ CXCL4: "
Interestingly, CXCL4 mediated down-regulation of CCR1, CCR2 and CCR5 was strongly dependent on the chemokine 's ability to stimulate autocrine/paracrine release of TNF-a
"
CCR2 ⊣ CXCL4: "
Interestingly, CXCL4 mediated down-regulation of CCR1, CCR2 and CCR5 was strongly dependent on the chemokine 's ability to stimulate autocrine/paracrine release of TNF-a
"
CCR5 ⊣ CXCL4: "
Interestingly, CXCL4 mediated down-regulation of CCR1, CCR2 and CCR5 was strongly dependent on the chemokine 's ability to stimulate autocrine/paracrine release of TNF-a
"
CCR ⊣ CXCL4: "
Culture supernatants of CXCL4 stimulated monocytes as well as chemokine enriched preparations thereof reproduced CXCL4 induced CCR down-regulation
"
Manually curated Databases
No curated data.