Administration of exogenous fractalkine, a CX3C chemokine, is capable of modulating inflammatory response in cecal ligation and puncture-induced sepsis.
Fractalkine (FTK) is a unique member of the CX3C chemokine family by acting through the CX3CR1 receptor. Membrane-bound FTK acts like an adhesion molecule, whereas soluble FTK (sFTK) acts as a classic chemokine ligand. Whether this chemokine plays a role in sepsis is still not clear. Using a mouse model of cecal ligation and puncture (CLP)-induced sepsis, we found that FTK levels were elevated in plasma 24 h after CLP. Reverse transcription-polymerase chain reaction results showed that FTK messenger RNA levels were upregulated, whereas CX3CR1 messenger RNA levels were downregulated in lungs after CLP procedure. To study the role of FTK in lung injury during sepsis, we injected exogenous sFTK into the mice before the CLP procedure. We found that plasma FTK levels were further elevated by sFTK. Mice that were injected with FTK had a lower myeloperoxidase activity in lungs compared with the CLP group. Furthermore, macrophage inflammatory protein 2, IL-1beta, and IL-6 levels in lungs were reduced after the injection of FTK. Treatment with sFTK also attenuated lung morphological changes in histological sections. To find out whether sFTK had an effect on leukocyte rolling and adherence, intravital microscope was used. Results showed that sFTK significantly attenuated leukocyte adhesion but had little effect on leukocyte rolling in mesenteric microcirculation. Taken together, our findings suggest that FTK may be a novel chemokine that modulates neutrophil infiltration and chemokine and cytokine production during sepsis.
He
Min
M
Department of Pharmacology and Cardiovascular Biology Research Group, National University of Singapore.
Moochhala
Shabbir M
SM
Adhikari
Sharmila
S
Bhatia
Madhav
M
D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D002448:Cell Adhesion / Q000187:drug effects; D054428:Chemokine CX3CL1 / Q000097:blood / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D036904:Leukocyte Rolling / Q000187:drug effects; D008168:Lung / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000097:blood* / Q000473:pathology; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects*; D009195:Peroxidase / Q000097:blood; D012333:RNA, Messenger / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D018805:Sepsis / Q000097:blood* / Q000473:pathology; D013152:Splanchnic Circulation / Q000187:drug effects; D013997:Time Factors
D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse; C471885:Cx3cr1 protein, mouse; D016207:Cytokines; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D009195:Peroxidase