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Neutrophil reverse migration becomes transparent with zebrafish.

Starnes TW, Huttenlocher A - Adv Hematol (2012)

Bottom Line: In vivo imaging studies in zebrafish, and more recently in mice, have made the novel observation that neutrophils leave a site of inflammation through a process called neutrophil reverse migration.The application of advanced imaging techniques to the genetically tractable, optically transparent zebrafish larvae was critical for these advances.Still, the mechanisms underlying neutrophil reverse migration and its effects on the resolution or priming of immune responses remain unclear.

View Article: PubMed Central - PubMed

Affiliation: Microbiology Doctoral Training Program and Medical Scientist Training Program, University of Wisconsin-Madison, Madison, WI 53706, USA.

ABSTRACT
The precise control of neutrophil-mediated inflammation is critical for both host defense and the prevention of immunopathology. In vivo imaging studies in zebrafish, and more recently in mice, have made the novel observation that neutrophils leave a site of inflammation through a process called neutrophil reverse migration. The application of advanced imaging techniques to the genetically tractable, optically transparent zebrafish larvae was critical for these advances. Still, the mechanisms underlying neutrophil reverse migration and its effects on the resolution or priming of immune responses remain unclear. Here, we review the current knowledge of neutrophil reverse migration, its potential roles in host immunity, and the live imaging tools that make zebrafish a valuable model for increasing our knowledge of neutrophil behavior in vivo.

No MeSH data available.


Related in: MedlinePlus

Proposed mechanisms for reversed migration. This diagram illustrates how chemoattractant gradients from the blood (red), endothelium (purple), and wound (green) or chemorepellent gradients (orange) may influence reverse migration. The color of a chemoattractant receptor matches the gradient to which it responds. (a)–(d) Reverse migration in the early wound response. (a) Demonstration of neutrophil reverse migration towards blood or endothelium-derived chemoattractants. (b) Reverse migration of a neutrophil away from a wound-derived chemorepellent. There could be competition between wound-derived chemoattractants (not shown) and chemorepellents promoting reverse migration, or neutrophils may perform fugetaxis from areas of high chemoattractant concentration. (c) Oscillatory behavior of neutrophils suggests competing gradients of chemoattractants may exist between the wound and vasculature. (d) Receptor desensitization, via internalization or other mechanisms, may allow neutrophils to oscillate between the wound and the vasculature while others are still actively responding to the wound. (e)–(f) Mechanisms that promote resolution of neutrophil-mediated inflammation at wounds. (e) During the healing phase, wounded tissue may gradually produce less neutrophil chemoattractant, shifting the balance to favor reverse migration. (f) Neutrophils that responded to a wound may initiate transcriptional changes favoring reverse migration from the wound. Potential changes include altered expression or sensitivity of chemoattractant receptors.
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fig2: Proposed mechanisms for reversed migration. This diagram illustrates how chemoattractant gradients from the blood (red), endothelium (purple), and wound (green) or chemorepellent gradients (orange) may influence reverse migration. The color of a chemoattractant receptor matches the gradient to which it responds. (a)–(d) Reverse migration in the early wound response. (a) Demonstration of neutrophil reverse migration towards blood or endothelium-derived chemoattractants. (b) Reverse migration of a neutrophil away from a wound-derived chemorepellent. There could be competition between wound-derived chemoattractants (not shown) and chemorepellents promoting reverse migration, or neutrophils may perform fugetaxis from areas of high chemoattractant concentration. (c) Oscillatory behavior of neutrophils suggests competing gradients of chemoattractants may exist between the wound and vasculature. (d) Receptor desensitization, via internalization or other mechanisms, may allow neutrophils to oscillate between the wound and the vasculature while others are still actively responding to the wound. (e)–(f) Mechanisms that promote resolution of neutrophil-mediated inflammation at wounds. (e) During the healing phase, wounded tissue may gradually produce less neutrophil chemoattractant, shifting the balance to favor reverse migration. (f) Neutrophils that responded to a wound may initiate transcriptional changes favoring reverse migration from the wound. Potential changes include altered expression or sensitivity of chemoattractant receptors.

Mentions: We speculate that the signals that trigger neutrophils to perform reverse migration could include a competing chemoattractant “pulling” them away from the wound, a chemorepellent “pushing” them away from the would, or both (Figures 2(a) and 2(b)). Because neutrophils often migrate back to the vasculature after an inflammatory response, chemoattractants emanating from the blood or endothelium are attractive targets for promoting migration away from a wound (Figure 2(a)). Interestingly, high concentrations of chemoattractants, including IL-8 (CXCL8), can repel neutrophils in vitro and in vivo [58]. Other leukocytes can also be repelled by high chemokine concentrations. T cells are repelled by high concentrations of SDF-1 (CXCL12) in vivo and in vitro [59], and monocytes can be repelled by high concentrations of eotaxin-3 (CCL26) [60]. Thus, it is also plausible that the wounded tissue could be a source of both chemoattractants and chemorepellents in competition with each other. Previous studies of leukocyte chemorepulsion suggest that a wound chemoattractant at sufficiently high concentration could also act as a chemorepellent. As a neutrophil approached the wounded tissue, the concentration of chemorepellent would increase, potentially overwhelming the effect of the chemoattractant and driving the neutrophil away from the wound (Figure 2(b)).


Neutrophil reverse migration becomes transparent with zebrafish.

Starnes TW, Huttenlocher A - Adv Hematol (2012)

Proposed mechanisms for reversed migration. This diagram illustrates how chemoattractant gradients from the blood (red), endothelium (purple), and wound (green) or chemorepellent gradients (orange) may influence reverse migration. The color of a chemoattractant receptor matches the gradient to which it responds. (a)–(d) Reverse migration in the early wound response. (a) Demonstration of neutrophil reverse migration towards blood or endothelium-derived chemoattractants. (b) Reverse migration of a neutrophil away from a wound-derived chemorepellent. There could be competition between wound-derived chemoattractants (not shown) and chemorepellents promoting reverse migration, or neutrophils may perform fugetaxis from areas of high chemoattractant concentration. (c) Oscillatory behavior of neutrophils suggests competing gradients of chemoattractants may exist between the wound and vasculature. (d) Receptor desensitization, via internalization or other mechanisms, may allow neutrophils to oscillate between the wound and the vasculature while others are still actively responding to the wound. (e)–(f) Mechanisms that promote resolution of neutrophil-mediated inflammation at wounds. (e) During the healing phase, wounded tissue may gradually produce less neutrophil chemoattractant, shifting the balance to favor reverse migration. (f) Neutrophils that responded to a wound may initiate transcriptional changes favoring reverse migration from the wound. Potential changes include altered expression or sensitivity of chemoattractant receptors.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig2: Proposed mechanisms for reversed migration. This diagram illustrates how chemoattractant gradients from the blood (red), endothelium (purple), and wound (green) or chemorepellent gradients (orange) may influence reverse migration. The color of a chemoattractant receptor matches the gradient to which it responds. (a)–(d) Reverse migration in the early wound response. (a) Demonstration of neutrophil reverse migration towards blood or endothelium-derived chemoattractants. (b) Reverse migration of a neutrophil away from a wound-derived chemorepellent. There could be competition between wound-derived chemoattractants (not shown) and chemorepellents promoting reverse migration, or neutrophils may perform fugetaxis from areas of high chemoattractant concentration. (c) Oscillatory behavior of neutrophils suggests competing gradients of chemoattractants may exist between the wound and vasculature. (d) Receptor desensitization, via internalization or other mechanisms, may allow neutrophils to oscillate between the wound and the vasculature while others are still actively responding to the wound. (e)–(f) Mechanisms that promote resolution of neutrophil-mediated inflammation at wounds. (e) During the healing phase, wounded tissue may gradually produce less neutrophil chemoattractant, shifting the balance to favor reverse migration. (f) Neutrophils that responded to a wound may initiate transcriptional changes favoring reverse migration from the wound. Potential changes include altered expression or sensitivity of chemoattractant receptors.
Mentions: We speculate that the signals that trigger neutrophils to perform reverse migration could include a competing chemoattractant “pulling” them away from the wound, a chemorepellent “pushing” them away from the would, or both (Figures 2(a) and 2(b)). Because neutrophils often migrate back to the vasculature after an inflammatory response, chemoattractants emanating from the blood or endothelium are attractive targets for promoting migration away from a wound (Figure 2(a)). Interestingly, high concentrations of chemoattractants, including IL-8 (CXCL8), can repel neutrophils in vitro and in vivo [58]. Other leukocytes can also be repelled by high chemokine concentrations. T cells are repelled by high concentrations of SDF-1 (CXCL12) in vivo and in vitro [59], and monocytes can be repelled by high concentrations of eotaxin-3 (CCL26) [60]. Thus, it is also plausible that the wounded tissue could be a source of both chemoattractants and chemorepellents in competition with each other. Previous studies of leukocyte chemorepulsion suggest that a wound chemoattractant at sufficiently high concentration could also act as a chemorepellent. As a neutrophil approached the wounded tissue, the concentration of chemorepellent would increase, potentially overwhelming the effect of the chemoattractant and driving the neutrophil away from the wound (Figure 2(b)).

Bottom Line: In vivo imaging studies in zebrafish, and more recently in mice, have made the novel observation that neutrophils leave a site of inflammation through a process called neutrophil reverse migration.The application of advanced imaging techniques to the genetically tractable, optically transparent zebrafish larvae was critical for these advances.Still, the mechanisms underlying neutrophil reverse migration and its effects on the resolution or priming of immune responses remain unclear.

View Article: PubMed Central - PubMed

Affiliation: Microbiology Doctoral Training Program and Medical Scientist Training Program, University of Wisconsin-Madison, Madison, WI 53706, USA.

ABSTRACT
The precise control of neutrophil-mediated inflammation is critical for both host defense and the prevention of immunopathology. In vivo imaging studies in zebrafish, and more recently in mice, have made the novel observation that neutrophils leave a site of inflammation through a process called neutrophil reverse migration. The application of advanced imaging techniques to the genetically tractable, optically transparent zebrafish larvae was critical for these advances. Still, the mechanisms underlying neutrophil reverse migration and its effects on the resolution or priming of immune responses remain unclear. Here, we review the current knowledge of neutrophil reverse migration, its potential roles in host immunity, and the live imaging tools that make zebrafish a valuable model for increasing our knowledge of neutrophil behavior in vivo.

No MeSH data available.


Related in: MedlinePlus