Resistin: a newly identified chemokine for human CD4-positive lymphocytes.
OBJECTIVE
Increased levels of resistin, a peptide secreted by adipocytes and inflammatory cells, circulate in patients with insulin resistance and early type 2 diabetes, a high-risk population for the development of a diffuse and extensive pattern of arteriosclerosis. Recent data suggest that resistin may activate vascular cells such as smooth muscle cells and endothelial cells, but hitherto nothing is known about the role of resistin in CD4-positive lymphocytes. Therefore, the present study examined the effect of resistin on CD4-positive lymphocyte migration, an important process in early atherogenesis.


RESULTS
Resistin stimulated CD4-positive cell chemotaxis in a concentration-dependent manner with a maximal induction of 2.25 +/- 0.54 at 100 ng/mL (P < 0.05, n = 7). This process involves pertussis toxin-sensitive G-proteins as well as activation of Src- and phosphoinositide 3-kinase (PI 3-K). Biochemical analysis showed that resistin induces phosphorylation of Src and PI 3-K activation in human CD4-positive cells. In addition, resistin activates RhoA, Rac-1, and Cdc42 in these cells as shown by affinity precipitation experiments. Finally, resistin-induced phosphorylation of myosin light chain was inhibited by Src short interference RNA transfection, underscoring the importance of the upstream signalling molecule Src in resistin-induced migration.


CONCLUSIONS
These data support an active role of resistin in CD4-positive lymphocyte chemotaxis and elucidate molecular mechanisms in resistin-induced cell migration.
Walcher
Daniel
D
Department of Internal Medicine II-Cardiology, University of Ulm, D-89081 Ulm, Germany.
Hess
Katharina
K
Berger
Rebecca
R
Aleksic
Milos
M
Heinz
Philipp
P
Bach
Helga
H
Durst
Renate
R
Hausauer
Angelina
A
Hombach
Vinzenz
V
Marx
Nikolaus
N
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D054461:Lim Kinases / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D052243:Resistin / Q000494:pharmacology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D054462:p21-Activated Kinases / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000502:physiology
D018925:Chemokines; D018994:Myosin Light Chains; C499624:RETN protein, human; D052243:Resistin; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases; C515892:LIMK1 protein, human; D054461:Lim Kinases; D054462:p21-Activated Kinases; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein