Modulation of CXC chemokine receptor expression and function in human neutrophils during aging in vitro suggests a role in their clearance from circulation
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Modulation of CXC chemokine receptor expression and function in human neutrophils during aging in vitro suggests a role in their clearance from circulation. / Weisel, Katja C; Bautz, Frank; Seitz, Gabriele; Yildirim, Sedat; Kanz, Lothar; Möhle, Robert.
in: MEDIAT INFLAMM, Jahrgang 2009, 2009, S. 790174.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Modulation of CXC chemokine receptor expression and function in human neutrophils during aging in vitro suggests a role in their clearance from circulation
AU - Weisel, Katja C
AU - Bautz, Frank
AU - Seitz, Gabriele
AU - Yildirim, Sedat
AU - Kanz, Lothar
AU - Möhle, Robert
PY - 2009
Y1 - 2009
N2 - In mice, differential regulation of CXC chemokine receptor expression in circulating polymorphonuclear neutrophils (PMNs) undergoing senescence results in homing to the bone marrow. However, the role of this compartment and of the chemokine receptor CXCR4 is still under discussion, and only scarce data exist about CXCR4 function in human PMN. In our study, we provide evidence that also in human neutrophils, expression (cell surface and mRNA), chemotactic and signaling functions of the homing-related chemokine receptor CXCR4 are upregulated during aging in vitro, independent of addition of stimulatory cytokines (TNF, IL-1, IL-8, G-CSF). In contrast, interleukin-8 receptors are downmodulated (CXCR2) or remain unchanged (CXCR1), suggesting that human PMNs undergoing senescence acquire a phenotype that impairs inflammatory extravasation and favors homing to the bone marrow or other tissues involved in sequestration. Partially retained responsiveness to interleukin-8 may be important for neutrophil function when senescence occurs after extravasation in inflamed tissues.
AB - In mice, differential regulation of CXC chemokine receptor expression in circulating polymorphonuclear neutrophils (PMNs) undergoing senescence results in homing to the bone marrow. However, the role of this compartment and of the chemokine receptor CXCR4 is still under discussion, and only scarce data exist about CXCR4 function in human PMN. In our study, we provide evidence that also in human neutrophils, expression (cell surface and mRNA), chemotactic and signaling functions of the homing-related chemokine receptor CXCR4 are upregulated during aging in vitro, independent of addition of stimulatory cytokines (TNF, IL-1, IL-8, G-CSF). In contrast, interleukin-8 receptors are downmodulated (CXCR2) or remain unchanged (CXCR1), suggesting that human PMNs undergoing senescence acquire a phenotype that impairs inflammatory extravasation and favors homing to the bone marrow or other tissues involved in sequestration. Partially retained responsiveness to interleukin-8 may be important for neutrophil function when senescence occurs after extravasation in inflamed tissues.
KW - Cell Line
KW - Cell Membrane
KW - Cell Movement
KW - Cellular Senescence
KW - Chemokine CXCL12
KW - Humans
KW - MAP Kinase Signaling System
KW - Mitogen-Activated Protein Kinase 1
KW - Mitogen-Activated Protein Kinase 3
KW - Neutrophils
KW - RNA, Messenger
KW - Receptors, CXCR
KW - Receptors, CXCR4
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1155/2009/790174
DO - 10.1155/2009/790174
M3 - SCORING: Journal article
C2 - 19390584
VL - 2009
SP - 790174
JO - MEDIAT INFLAMM
JF - MEDIAT INFLAMM
SN - 0962-9351
ER -