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A Novel Function for Chemokines: Downregulation of Neutrophil Migration
Author(s) -
Lang K.,
Hatt H.,
Niggemann B.,
Zaenker K. S.,
Entschladen F.
Publication year - 2003
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.2003.01247.x
Subject(s) - adenylyl cyclase , microbiology and biotechnology , chemokine , chemotaxis , population , calcium in biology , calcium , phospholipase c , chemistry , cell migration , signal transduction , biology , intracellular , biochemistry , immune system , immunology , cell , receptor , medicine , environmental health , organic chemistry
Migration is a key function of stem cells during ontogenesis, of fibroblasts in wound healing and of immune cells in host defence. The signals that initiate migration are as important as signals that terminate migration, once the destination has been reached. We now show that formyl‐methionyl‐leucyl‐phenylalanine (fMLP)‐induced migration of neutrophils was inhibited by increasing concentrations of interleukin‐8 (IL‐8). IL‐8 dose dependently increased the frequency and the duration of stop‐periods, whereas the percentage of cells of a population that was locomotory active remained constant. The stop‐signal delivered by IL‐8 was intracellularly transduced by a dichotomic pathway: (i) the activation of the adenylyl cyclase leads to an increase of cytosolic cyclic adenosine monophosphate, which results in an activation of the sarcoplasmatic/endoplasmatic reticulum calcium ATPase pump and a calcium sequestration; (ii) the activation of the phospholipase Cβ (PLCβ) generates inositol‐1,4,5‐phosphate (IP 3 ) and diacylglycerol (DAG), which results in IP 3 ‐mediated release of intracellularly stored calcium in the endoplasmatic reticulum and DAG‐mediated activation of protein kinase C. Thus, we show for the first time that a chemokine, IL‐8, in concert with fMLP, downregulates the neutrophil migration through the regulation of the intracellular calcium concentration via the adenylyl cyclase and the PLCβ2.