Exogenous stromal cell-derived factor-1 induces modest leukocyte recruitment in vivo

2008 ◽  
Vol 294 (6) ◽  
pp. H2524-H2534 ◽  
Author(s):  
Steven M. Kerfoot ◽  
Graciela Andonegui ◽  
Claudine S. Bonder ◽  
Lixin Liu

Stromal cell-derived factor-1 (SDF-1; CXCL12), a CXC chemokine, has been found to be involved in inflammation models in vivo and in cell adhesion, migration, and chemotaxis in vitro. This study aimed to determine whether exogenous SDF-1 induces leukocyte recruitment in mice. After systemic administration of SDF-1α, expression of the adhesion molecules P-selectin and VCAM-1 in mice was measured using a quantitative dual-radiolabeled Ab assay and leukocyte recruitment in various tissues was evaluated using intravital microscopy. The effect of local SDF-1α on leukocyte recruitment was also determined in cremaster muscle and compared with the effect of the cytokine TNFα and the CXC chemokine keratinocyte-derived chemokine (KC; CXCL1). Systemic administration of SDF-1α (10 μg, 4–5 h) induced upregulation of P-selectin, but not VCAM-1, in most tissues in mice. It caused modest leukocyte recruitment responses in microvasculature of cremaster muscle, intestine, and brain, i.e., an increase in flux of rolling leukocytes in cremaster muscle and intestines, leukocyte adhesion in all three tissues, and emigration in cremaster muscle. Local treatment with SDF-1α (1 μg, 4–5 h) reduced leukocyte rolling velocity and increased leukocyte adhesion and emigration in cremasteric venules, but the responses were much less profound than those elicited by KC or TNFα. SDF-1α-induced recruitment was dependent on endothelial P-selectin, but not P-selectin on platelets. We conclude that the exogenous SDF-1α enhances leukocyte-endothelial cell interactions and induces modest and endothelial P-selectin-dependent leukocyte recruitment.

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Kirsten Buschmann ◽  
Johannes Poeschl ◽  
Natascha Braach ◽  
Hannes Hudalla ◽  
Navina Kuss ◽  
...  

Although fish oil-based and olive oil-based lipid emulsions have been shown to exert anti-inflammatory functions, the immunomodulating properties of lipids are still controversial. Therefore, we investigated the anti-inflammatory effect of three different parenterally administered lipid emulsions in vivo: olive oil-based Clinoleic, fish oil-based Smoflipid, and soybean oil-based Lipofundin. We observed leukocyte recruitment in inflamed murine cremaster muscle using intravital microscopy and survival in a murine model of LPS-induced systemic inflammation and analyzed expression of leukocyte and endothelial adhesion molecules. Olive oil-based Clinoleic and fish oil-based Smoflipid profoundly inhibited leukocyte adhesion compared to Lipofundin during LPS-induced inflammation of the murine cremaster muscle. In the trauma model of cremaster muscle inflammation, Lipofundin was the only lipid emulsion that even augmented leukocyte adhesion. In contrast to Smoflipid and Lipofundin, Clinoleic effectively blocked leukocyte recruitment and increased survival during lethal endotoxemia. Flow chamber experiments and analysis of adhesion molecule expression suggest that both endothelial and leukocyte driven mechanisms might contribute to anti-inflammatory effects of Clinoleic. We conclude that the anti-inflammatory properties of Clinoleic are superior to those of Smoflipid and Lipofundin even during systemic inflammation. Thus, these results should stimulate further studies investigating parenteral lipids as an anti-inflammatory strategy in critically ill patients.


2010 ◽  
Vol 19 (4) ◽  
pp. 399-408 ◽  
Author(s):  
Sina Y. Rabbany ◽  
Joseph Pastore ◽  
Masaya Yamamoto ◽  
Tim Miller ◽  
Shahin Rafii ◽  
...  

Proper wound diagnosis and management is an increasingly important clinical challenge and is a large and growing unmet need. Pressure ulcers, hard-to-heal wounds, and problematic surgical incisions are emerging at increasing frequencies. At present, the wound-healing industry is experiencing a paradigm shift towards innovative treatments that exploit nanotechnology, biomaterials, and biologics. Our study utilized an alginate hydrogel patch to deliver stromal cell-derived factor-1 (SDF-1), a naturally occurring chemokine that is rapidly overexpressed in response to tissue injury, to assess the potential effects SDF-1 therapy on wound closure rates and scar formation. Alginate patches were loaded with either purified recombinant human SDF-1 protein or plasmid expressing SDF-1 and the kinetics of SDF-1 release were measured both in vitro and in vivo in mice. Our studies demonstrate that although SDF-1 plasmid- and protein-loaded patches were able to release therapeutic product over hours to days, SDF-1 protein was released faster (in vivo Kd 0.55 days) than SDF-1 plasmid (in vivo Kd 3.67 days). We hypothesized that chronic SDF-1 delivery would be more effective in accelerating the rate of dermal wound closure in Yorkshire pigs with acute surgical wounds, a model that closely mimics human wound healing. Wounds treated with SDF-1 protein ( n = 10) and plasmid ( n = 6) loaded patches healed faster than sham ( n = 4) or control ( n = 4). At day 9, SDF-1-treated wounds significantly accelerated wound closure (55.0 ± 14.3% healed) compared to nontreated controls (8.2 ± 6.0%, p < 0.05). Furthermore, 38% of SDF-1-treated wounds were fully healed at day 9 (vs. none in controls) with very little evidence of scarring. These data suggest that patch-mediated SDF-1 delivery may ultimately provide a novel therapy for accelerating healing and reducing scarring in clinical wounds.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Mizuko Osaka ◽  
Sumihiko Hagita ◽  
Masayuki Yoshida

Objective. To monitor the anti-inflammatory effect of rosuvastatin in leukocyte endothelial interactions in the atheroprone femoral artery in vivo.Methods and Results. Male Apolipoprotein E null mice (ApoE−/− mice, 6 weeks old) were fed a high-fat diet (20% fat, 1.25% cholesterol) with or without the HMG CoA reductase inhibitor rosuvastatin (10 mg/kg/day) for 6 weeks. Significant leukocyte adhesion was observed in the femoral artery of ApoE−/− mice, but not of wild type mice, in the absence of rosuvastatin. Interestingly, no obvious plaque formation was observed in the artery at this time point. The number of adherent leukocytes was dramatically diminished in ApoE−/− mice treated with rosuvastatin. DHE-associated oxidative stress and the expression of gp91-phox, a component of NADPH oxidase, were induced in ApoE−/− mice and were abolished by rosuvastatin treatment.Conclusion. Our data documented leukocyte recruitment prior to lipid accumulation and subsequent inhibition by rosuvastatin. The underlying mechanism seemed to involve oxidative stress and an anti-inflammatory effect on the endothelium of atheroprone vessels.


2019 ◽  
Vol 47 (11) ◽  
pp. 5426-5440
Author(s):  
Zejia Sun ◽  
Xin Li ◽  
Xiang Zheng ◽  
Peng Cao ◽  
Baozhong Yu ◽  
...  

Stem cell therapy has shown promise in treating a variety of pathologies, such as myocardial infarction, ischaemic stroke and organ transplantation. The stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) axis plays a key role in stem cell mobilization. This review describes the important role of SDF-1 in tissue injury and how it works in tissue revascularization and regeneration via CXCR4. Furthermore, factors influencing the SDF-1/CXCR4 axis and its clinical potential in ischaemia reperfusion injury, such as renal transplantation, are discussed. Exploring signalling pathways of the SDF-1/CXCR4 axis will contribute to the development of stem cell therapy so that more clinical problems can be solved. Controlling directional homing of stem cells through the SDF-1/CXCR4 axis is key to improving the efficacy of stem cell therapy for tissue injury. CXCR4 antagonists may also be effective in increasing circulating levels of adult stem cells, thereby exerting beneficial effects on damaged or inflamed tissues in diseases that are currently not treated by standard approaches.


2002 ◽  
Vol 283 (1) ◽  
pp. G196-G203 ◽  
Author(s):  
John Wong ◽  
Paul Kubes ◽  
Yikun Zhang ◽  
Yang Li ◽  
Stefan J. Urbanski ◽  
...  

The pathogenesis of hepatic allograft rejection remains unclear. We aimed to clarify the early role of intercellular adhesion molecule-1 (ICAM-1)-mediated cell recruitment in chronic hepatic rejection. Liver transplantation was performed from Lewis to Lewis rats (isograft controls) and from Lewis to Brown Norway rats (allograft rejection group). The allografted rats were treated with either ICAM-1 antisense oligonucleotides (10 mg · kg−1· day−1× 6 days ip) or a control preparation (either ICAM-1 missense oligonucleotide or normal saline). Hepatic leukocyte recruitment in vivo was studied on day 6 by using intravital microscopy. Liver histology, biochemistry, and survival rates were also examined. Leukocyte adhesion in terminal hepatic venules was significantly increased in the rejection group compared with isograft controls. Antisense ICAM-1 in the allografted group effectively reduced leukocyte adhesion. Histology and liver chemistry were less deranged in the antisense-treated groups compared with control-treated allografted rats. In the allograft groups, survival was significantly prolonged in the antisense-treated rats (42.3 ± 1.2 days) compared with the controls (25.2 ± 2.7 days). These results showed that early leukocyte recruitment in the hepatic microvasculature of rejecting allografts is ICAM-1 dependent and suggest that impacting on early cell recruitment can significantly ameliorate chronic rejection.


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