Redox and Src family kinase signaling control leukocyte wound attraction and neutrophil reverse migration

Tissue damage induces early recruitment of neutrophils through redox-regulated Src family kinase (SFK) signaling in neutrophils. Redox-SFK signaling in epithelium is also necessary for wound resolution and tissue regeneration. How neutrophil-mediated inflammation resolves remains unclear. In this paper, we studied the interactions between macrophages and neutrophils in response to tissue damage in zebrafish and found that macrophages contact neutrophils and induce resolution via neutrophil reverse migration. We found that redox-SFK signaling through p22phox and Yes-related kinase is necessary for macrophage wound attraction and the subsequent reverse migration of neutrophils. Importantly, macrophage-specific reconstitution of p22phox revealed that macrophage redox signaling is necessary for neutrophil reverse migration. Thus, redox-SFK signaling in adjacent tissues is essential for coordinated leukocyte wound attraction and repulsion through pathways that involve contact-mediated guidance.

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Inhibiting EGF Receptor or SRC Family Kinase Signaling Overcomes BRAF Inhibitor Resistance in Melanoma

Cancer Discovery ◽

10.1158/2159-8290.cd-12-0386 ◽

2012 ◽

Vol 3 (2) ◽

pp. 158-167 ◽

Cited By ~ 219

Author(s):

Maria R. Girotti ◽

Malin Pedersen ◽

Berta Sanchez-Laorden ◽

Amaya Viros ◽

Samra Turajlic ◽

...

Keyword(s):

Egf Receptor ◽

Braf Inhibitor ◽

Kinase Signaling ◽

Src Family Kinase ◽

Inhibitor Resistance

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Src-family kinase signaling, actin-mediated membrane trafficking and organellar dynamics in the control of cell fate: Lessons to be learned from the adenovirus E4orf4 death factor

Cellular Signalling ◽

10.1016/j.cellsig.2010.04.007 ◽

2010 ◽

Vol 22 (11) ◽

pp. 1604-1614 ◽

Cited By ~ 13

Author(s):

Josée N. Lavoie ◽

Marie-Claude Landry ◽

Robert L. Faure ◽

Claudia Champagne

Keyword(s):

Cell Fate ◽

Membrane Trafficking ◽

Kinase Signaling ◽

Src Family Kinase

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Immunomodulatory Functions of Mesenchymal Stem Cells in Tissue Engineering

Stem Cells International ◽

10.1155/2019/9671206 ◽

2019 ◽

Vol 2019 ◽

pp. 1-18 ◽

Cited By ~ 14

Author(s):

Haojiang Li ◽

Shi Shen ◽

Haitao Fu ◽

Zhenyong Wang ◽

Xu Li ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Tissue Regeneration ◽

Tissue Damage ◽

Material Selection ◽

Immune Microenvironment ◽

Chronic Injury ◽

Research Fields

The inflammatory response to chronic injury affects tissue regeneration and has become an important factor influencing the prognosis of patients. In previous stem cell treatments, it was revealed that stem cells not only have the ability for direct differentiation or regeneration in chronic tissue damage but also have a regulatory effect on the immune microenvironment. Stem cells can regulate the immune microenvironment during tissue repair and provide a good “soil” for tissue regeneration. In the current study, the regulation of immune cells by mesenchymal stem cells (MSCs) in the local tissue microenvironment and the tissue damage repair mechanisms are revealed. The application of the concepts of “seed” and “soil” has opened up new research avenues for regenerative medicine. Tissue engineering (TE) technology has been used in multiple tissues and organs using its biomimetic and cellular cell abilities, and scaffolds are now seen as an important part of building seed cell microenvironments. The effect of tissue engineering techniques on stem cell immune regulation is related to the shape and structure of the scaffold, the preinflammatory microenvironment constructed by the implanted scaffold, and the material selection of the scaffold. In the application of scaffold, stem cell technology has important applications in cartilage, bone, heart, and liver and other research fields. In this review, we separately explore the mechanism of MSCs in different tissue and organs through immunoregulation for tissue regeneration and MSC combined with 3D scaffolds to promote MSC immunoregulation to repair damaged tissues.

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Early redox, Src family kinase, and calcium signaling integrate wound responses and tissue regeneration in zebrafish

The Journal of Cell Biology ◽

10.1083/jcb.201203154 ◽

2012 ◽

Vol 199 (2) ◽

pp. 225-234 ◽

Cited By ~ 126

Author(s):

Sa Kan Yoo ◽

Christina M. Freisinger ◽

Danny C. LeBert ◽

Anna Huttenlocher

Keyword(s):

Calcium Signaling ◽

Tissue Regeneration ◽

Tissue Injury ◽

Src Family Kinase ◽

Fin Regeneration ◽

Epimorphic Regeneration ◽

Zebrafish Larvae ◽

Redox Sensor ◽

Wound Responses ◽

Early Wound

Tissue injury can lead to scar formation or tissue regeneration. How regenerative animals sense initial tissue injury and transform wound signals into regenerative growth is an unresolved question. Previously, we found that the Src family kinase (SFK) Lyn functions as a redox sensor in leukocytes that detects H2O2 at wounds in zebrafish larvae. In this paper, using zebrafish larval tail fins as a model, we find that wounding rapidly activated SFK and calcium signaling in epithelia. The immediate SFK and calcium signaling in epithelia was important for late epimorphic regeneration of amputated fins. Wound-induced activation of SFKs in epithelia was dependent on injury-generated H2O2. A SFK member, Fynb, was responsible for fin regeneration. This work provides a new link between early wound responses and late regeneration and suggests that redox, SFK, and calcium signaling are immediate “wound signals” that integrate early wound responses and late epimorphic regeneration.

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Multiplex Analysis of Src Family Kinase Signaling by Microbead Suspension Arrays

Assay and Drug Development Technologies ◽

10.1089/adt.2009.0255 ◽

2010 ◽

Vol 8 (4) ◽

pp. 488-496 ◽

Cited By ~ 5

Author(s):

Mel Campbell ◽

Wen-Rong Lie ◽

Jing Zhao ◽

David Hayes ◽

Jehangir Mistry ◽

...

Keyword(s):

Kinase Signaling ◽

Src Family Kinase ◽

Multiplex Analysis

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Molecular interdiction of Src-family kinase signaling in hematopoietic cells

Oncogene ◽

10.1038/sj.onc.1208078 ◽

2004 ◽

Vol 23 (48) ◽

pp. 8024-8032 ◽

Cited By ~ 15

Author(s):

Robert L Geahlen ◽

Misty D Handley ◽

Marietta L Harrison

Keyword(s):

Hematopoietic Cells ◽

Kinase Signaling ◽

Src Family Kinase

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The CXCL12/CXCR4 signalling axis retains neutrophils at inflammatory sites in zebrafish

10.1101/626978 ◽

2019 ◽

Cited By ~ 3

Author(s):

Hannah M. Isles ◽

Kimberly Herman ◽

Anne L. Robertson ◽

Catherine A. Loynes ◽

Lynne R. Prince ◽

...

Keyword(s):

Inflammatory Disease ◽

Tissue Damage ◽

Tissue Injury ◽

Transgenic Zebrafish ◽

Sequencing Data ◽

Cxcr4 Antagonist ◽

Reverse Migration ◽

Zebrafish Larvae ◽

Inflammation Resolution

AbstractThe inappropriate retention of neutrophils in the lung is a major driver of the excessive tissue damage characteristic of respiratory inflammatory diseases including COPD, ARDS and cystic fibrosis. The molecular programmes which orchestrate neutrophil recruitment to inflammatory sites through chemotactic guidance have been well studied. However, how neutrophil sensitivity to these cues is modulated during inflammation resolution is not understood. The identification of neutrophil reverse migration as a mechanism of inflammation resolution and the ability to modulate this therapeutically has identified a new target to treat inflammatory disease. Here we investigate the role of the CXCL12/CXCR4 signalling axis in modulating neutrophil retention at inflammatory sites. We used an in vivo tissue injury model to study inflammation using transgenic zebrafish larvae. Expression of cxcl12a and cxcr4b during the tissue damage response was assessed using in situ hybridisation and analysis of RNA sequencing data. CRISPR/Cas9 was used to knockdown cxcl12a and cxcr4b in zebrafish larvae. The CXCR4 antagonist AMD3100 was used to block the Cxcl12/Cxcr4 signalling axis pharmacologically. We identified that cxcr4b and cxcl12a are expressed at the wound site in zebrafish larvae during the inflammatory response. Following tail-fin transection, removal of neutrophils from inflammatory sites is significantly increased in cxcr4b and cxcl12a CRISPR knockdown larvae. Pharmacological inhibition of the Cxcl12/Cxcr4 signalling axis accelerates inflammation resolution, an effect caused by an increase in neutrophil reverse migration. The findings of this study suggest that CXCR4/CXCL12 signalling may play an important role in neutrophil retention at inflammatory sites, identifying a potential new target for the therapeutic removal of neutrophils from the lung in chronic inflammatory disease.

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M1-like macrophage contributes to chondrogenesis in vitro

Scientific Reports ◽

10.1038/s41598-021-00232-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yoshiyuki Miyamoto ◽

Keigo Kubota ◽

Yukiyo Asawa ◽

Kazuto Hoshi ◽

Atsuhiko Hikita

Keyword(s):

Regenerative Medicine ◽

Tissue Regeneration ◽

Tissue Damage ◽

Collagen Type ◽

Experimental System ◽

Cartilage Tissue ◽

Oral And Maxillofacial Regions

AbstractCartilage tissues have poor self-repairing abilities. Regenerative medicine can be applied to recover cartilage tissue damage in the oral and maxillofacial regions. However, hitherto it has not been possible to predict the maturity of the tissue construction after transplantation or to prepare mature cartilage tissues before transplantation that can meet clinical needs. Macrophages play an important role in cartilage tissue regeneration, although the exact mechanisms remain unknown. In this study, we established and verified an in vitro experimental system for the direct co-culture of cell pellets prepared from mouse auricular chondrocytes and macrophages polarized into four phenotypes (M1-like, M1, M2-like, and M2). We demonstrate that cartilage pellets co-cultured with M1-like promoted collagen type 2 and aggrecan production and induced the most significant increase in chondrogenesis. Furthermore, M1-like shifted to M2 on day 7 of co-culture, suggesting that the cartilage pellet supplied factors that changed the polarization of M1-like. Our findings suggest that cartilage regenerative medicine will be most effective if the maturation of cartilage tissues is induced in vitro by co-culture with M1-like before transplantation.

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