Neutrophil chemoattractants generated in two phases during reperfusion of ischemic myocardium in the rabbit. Evidence for a role for C5a and interleukin-8.

Ivey, Claire L.; Williams, Frances; Collins, Paul; Jose, Peter J.; Williams, Timothy J.

doi:10.1172/jci117974

Cited by 181 publications

(78 citation statements)

References 45 publications

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“…IL-8 upregulation has been documented in canine [102] and rabbit [103] models of experimental myocardial infarction. Elucidation of the role of IL-8 in cardiac injury has been hampered by the absence of an IL-8 homologue in mice.…”

Section: Chemokines In Healing Infarctionmentioning

confidence: 99%

The immune system and cardiac repair

Frangogiannis

2008

Pharmacological Research

568

499

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Myocardial infarction is the most common cause of cardiac injury and results in acute loss of a large number of myocardial cells. Because the heart has negligible regenerative capacity, cardiomyocyte death triggers a reparative response that ultimately results in formation of a scar and is associated with dilative remodeling of the ventricle. Cardiac injury activates innate immune mechanisms initiating an inflammatory reaction. Toll Like Receptor-mediated pathways, the complement cascade and reactive oxygen generation induce Nuclear Factor (NF)-κB activation and upregulate chemokine and cytokine synthesis in the infarcted heart. Chemokines stimulate the chemotactic recruitment of inflammatory leukocytes into the infarct, while cytokines promote adhesive interactions between leukocytes and endothelial cells, resulting in transmigration of inflammatory cells into the site of injury. Monocyte subsets play distinct roles in phagocytosis of dead cardiomyocytes and in granulation tissue formation through the release of growth factors. Clearance of dead cells and matrix debris may be essential for resolution of inflammation and transition into the reparative phase. Transforming Growth Factor (TGF)-β plays a crucial role in cardiac repair by suppressing inflammation while promoting myofibroblast phenotypic modulation and extracellular matrix deposition. Myofibroblast proliferation and angiogenesis result in formation of highly vascularized granulation tissue. As the healing infarct matures, fibroblasts become apoptotic and a collagen-based matrix is formed, while many infarct neovessels acquire a muscular coat and uncoated vessels regress. Timely resolution of the inflammatory infiltrate and spatial containment of the inflammatory and reparative response into the infarcted area are essential for optimal infarct healing. Targeting inflammatory pathways following infarction may reduce cardiomyocyte injury and attenuate adverse remodeling. In addition, understanding the role of the immune system in cardiac repair is necessary in order to design optimal strategies for cardiac regeneration.

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Section: Chemokines In Healing Infarctionmentioning

confidence: 99%

The immune system and cardiac repair

Frangogiannis

2008

Pharmacological Research

568

499

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“…This is the earliest cell adhesion event following tissue insult. [37][38][39][40] Activated neutrophils participate in the cleaning of the scar, but they can also in some cases be deleterious, increasing superoxide production, free radicals, and proinflammatory cytokines. 41 Using bone marrow transplantation, we overexpressed sFRP-1 specifically in leukocytes and compared its effect on the inflammatory processes, to that in overexpression in ECs or in cardiomyocytes.…”

Section: Sfrp-1 Effects In Vivomentioning

confidence: 99%

Secreted Frizzled-Related Protein-1 Improves Postinfarction Scar Formation Through a Modulation of Inflammatory Response

Barandon

Casassus

Leroux

et al. 2011

ATVB

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Objective-The inflammatory response after myocardial infarction plays a crucial role in the healing process. Lately, there is accumulating evidence that the Wnt/Frizzled pathway may play a distinct role in inflammation. We have shown that secreted frizzled-related protein-1 (sFRP-1) overexpression reduced postinfarction scar size, and we noticed a decrease in neutrophil infiltration in the ischemic tissue. We aimed to further elucidate the role of sFRP-1 in the postischemic inflammatory process. Methods and Results-We found that in vitro, sFRP-1 was able to block leukocyte activation and cytokine production. We transplanted bone marrow cells (BMCs) from transgenic mice overexpressing sFRP-1 into wild-type recipient mice and compared myocardial healing with that of mice transplanted with wild-type BMCs. These results were compared with those obtained in transgenic mice overexpressing sFRP-1 specifically in endothelial cells or in cardiomyocytes to better understand the spatiotemporal mechanism of the sFRP-1 effect. Our findings indicate that when overexpressed in the BMCs, but not in endothelial cells or cardiomyocytes, sFRP-1 was able to reduce neutrophil infiltration after ischemia, by switching the balance of pro-and antiinflammatory cytokine expression, leading to a reduction in scar formation and better cardiac hemodynamic parameters. Conclusion-sFRP-1 impaired the loop of cytokine amplification and decreased neutrophil activation and recruitment into the scar, without altering the neutrophil properties. These data support the notion that sFRP-1 may be a novel antiinflammatory factor protecting the heart from damage after myocardial infarction. (Arterioscler Thromb Vasc Biol. 2011;31:e80-e87.)

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“…In addition, others have shown that C5 and specifically, C5a, is critical for neutrophil and monocyte chemotaxis in either myocardial or mesenteric ischemic models (11)(12)(13)(14). Finally, in a renal ischemia/reperfusion model, C5a blockade prevents damage that is not dependent on neutrophil infiltration, but by alteration of the chemokine profile (13).…”

Section: Introductionmentioning

confidence: 99%