Signaling components involved in leptin-induced amplification of the atherosclerosis-related properties of human monocytes.
OBJECTIVE
Leptin, a 16-kDa cytokine that is released mainly by the adipose tissue, is known to affect a wide assortment of processes, ranging from energy homeostasis to angiogenesis and the immune response. In the present study, the effect of leptin on atherosclerosis-related properties of human monocytes was investigated. methods: Monocytes were isolated from whole blood obtained from healthy donors who had normal body mass index values. Pharmacological inhibition of specific signaling proteins was implemented. Fluorescence spectrometry and immunofluorescence techniques, as well as ELISA methods, were utilized. Leptin dose response curves were determined for each type of experiment.


RESULTS
Leptin (160 ng/ml) was found to augment monocyte adhesion to laminin-1 and its migration through this glycoprotein, which is one of the main components of the extracellular matrix. Additionally, leptin increased CD36-receptor surface expression, as well as moderately oxidized low-density lipoprotein (oxLDL(3)) uptake levels.


CONCLUSIONS
Leptin amplifies the pro-atheromatic properties of human monocytes through a complex signaling net which involves the Na(+)/H(+) exchanger isoform-1, the actin cytoskeleton, phosphoinositide 3-kinase, certain conventional isoforms of protein kinase C and NADPH oxidase.
Konstantinidis
Diamantis
D
Laboratory of Animal Physiology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Paletas
Konstantinos
K
Koliakos
George
G
Kaloyianni
Martha
M
D050197:Atherosclerosis / Q000209:etiology*; D018955:CD36 Antigens / Q000032:analysis; D027682:Cation Transport Proteins / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007797:Laminin / Q000502:physiology; D020738:Leptin / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D019255:NADPH Oxidases / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D015398:Signal Transduction; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology
D018955:CD36 Antigens; D027682:Cation Transport Proteins; D007797:Laminin; D020738:Leptin; D008077:Lipoproteins, LDL; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; C121346:laminin 1; C099252:oxidized low density lipoprotein; D019255:NADPH Oxidases; D019869:Phosphatidylinositol 3-Kinases