β1 Integrins Are Critically Involved in Neutrophil Locomotion in Extravascular Tissue In Vivo

Werr, Joachim; Xie, Xun; Hedqvist, Per; Ruoslahti, Erkki; Lindbom, Lennart

doi:10.1084/jem.187.12.2091

Cited by 144 publications

(125 citation statements)

References 27 publications

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“…Stimulated by a chemotactic gradient, leukocytes traverse the ECM by way of transient interactions between integrin receptors and components of the ECM and that serve as adhesive ligands (Lauffenburger and Horwitz, 1996;Palecek et al, 1997). Integrins have been known to contribute to the process of neutrophil locomotion include members of CD29 and CD18 (Gao and Issekutz, 1997;Werr et al, 1998;Imhof and Aurrand-Lions, 2004). CD29 also involves cell-tocell adhesion (Behzad et al, 1996;Werr et al, 1998), which may be important for the anchorage of the engrafted cells.…”

Section: Discussionmentioning

confidence: 99%

“…Integrins have been known to play a key role in cell adhesion, migration, and chemotaxis (Gao and Issekutz, 1997;Werr et al, 1998;Ridger et al, 2001a;Lindbom and Werr, 2002;Imhof and Aurrand-Lions, 2004). Localization of leukocytes to extravascular sites of inflammation is a func- tion of repeated adhesive and de-adhesive events.…”

Section: Discussionmentioning

confidence: 99%

“…Integrins have been known to contribute to the process of neutrophil locomotion include members of CD29 and CD18 (Gao and Issekutz, 1997;Werr et al, 1998;Imhof and Aurrand-Lions, 2004). CD29 also involves cell-tocell adhesion (Behzad et al, 1996;Werr et al, 1998), which may be important for the anchorage of the engrafted cells. We hypothesized that a similar mechanism was used for the engrafted BM-MSCs homing to the infarct.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Mesenchymal Stem Cells Use Integrin β1 Not CXC Chemokine Receptor 4 for Myocardial Migration and Engraftment

Huang

et al. 2007

MBoC

217

145

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Recent evidence has demonstrated the importance of bone marrow-derived mesenchymal stem cells (BM-MSCs) in the repair of damaged myocardium. The molecular mechanisms of engraftment and migration of BM-MSCs in the ischemic myocardium are unknown. In this study, we developed a functional genomics approach toward the identification of mediators of engraftment and migration of BM-MSCs within the ischemic myocardium. Our strategy involves microarray profiling (>22,000 probes) of ischemic hearts, complemented by reverse transcription-polymerase chain reaction and fluorescence-activated cell sorting of corresponding adhesion molecule and cytokine receptors in BM-MSCs to focus on the coexpressed pairs only. Our data revealed nine complementary adhesion molecules and cytokine receptors, including integrin ␤1, integrin ␣4, and CXC chemokine receptor 4 (CXCR4). To examine their functional contributions, we first blocked selectively these receptors by preincubation of BM-MSCs with specific neutralizing antibodies, and then we administered these cells intramyocardially. A significant reduction in the total number of BM-MSC in the infarcted myocardium was observed after integrin ␤1 blockade but not integrin ␣4 or CXCR4 blockade. The latter observation is distinctively different from that reported for hematopoietic stem cells (HSCs). Thus, our data show that BM-MSCs use a different pathway from HSCs for intramyocardial trafficking and engraftment. INTRODUCTIONCardiac repair and remodeling after ischemic injury involves myocyte hypertrophy, collagen deposition, and possibly ventricular dilatation (Sutton and Sharpe, 2000). Recent provocative data suggest that stem cells, either resident in the heart or originating from the bone marrow, may play an important role in the repair and regeneration of the injured myocardium (Anversa and Nadal-Ginard, 2002). We and others have shown that intramyocardial transplantation of bone marrow-derived stem cells (BMSCs) can promote cardiac repair with resulting functional improvement and reduced infarct size (Kocher et al., 2001;Mangi et al., 2003;Amado et al., 2005). In addition to direct transplantation, mobilization of BMSCs with cytokines such as granulocytecolony stimulating factor (G-CSF) and stem cell factor has been reported to enhance myocardial repair and improve cardiac function (Anversa and Nadal-Ginard, 2002;Askari et al., 2003). However, in a recent trial, the subcutaneous administration of G-CSF after acute myocardial infarction (MI) did not lead to further improvement in ventricular function compared with conventional treatment (Ripa et al., 2006). These controversial findings suggest the need to understand the molecular mechanisms involved with stem cell migration and engraftment into the infarcted myocardium.It has been reported that hematopoietic stem cells (HSCs) migrate in response to stromal-derived factor (SDF)-1␣, the ligand for the CXC chemokine receptor 4 (CXCR4) (Wright et al., 2002), and the up-regulation of SDF-1 in the ischemic myocardium mediates homing of HSCs vi...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mesenchymal Stem Cells Use Integrin β1 Not CXC Chemokine Receptor 4 for Myocardial Migration and Engraftment

Huang

et al. 2007

MBoC

217

145

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“…Several reports indicate that adhesion and transmigration mediate signals facilitating the migration through the basement membrane and interstitial matrix. Engagement of b2-integrins stimulated b1 integrin expression in neutrophils, resulting in an enhanced mobility of neutrophils in collagen I gels [11,12]. Ligation of CD31 on leukocytes can lead to the activation of b1-, b2-and b3-integrins [13,14].…”

Section: Introductionmentioning

confidence: 99%

Human Thy‐1 induces secretion of matrix metalloproteinase‐9 and CXCL8 from human neutrophils

et al. 2008

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Neutrophils are the first cells arriving at sites of acute inflammation. On their way from blood to the site of inflammation, neutrophils have to adhere to endothelial cells (EC), to transverse the basement membrane and subsequently to travel through the interstitial matrix. Recently, we have shown that human Thy-1 is an alternate EC receptor for the leukocyte integrin Mac-1 that contributes to leukocyte recruitment to sites of inflammation, providing a new pathway for adhesion and transmigration of neutrophils. Here, we studied the effect of Thy-1-mediated adhesion on neutrophil functions. Binding of neutrophils to recombinant human Thy-1 stimulated the release of MMP-9 from neutrophils, resulting in their enhanced migration through collagen-IV and matrigel. Further, we showed that neutrophil interaction with Thy-1 stimulated secretion of CXCL8 and thus could support the attraction of additional neutrophils to inflammatory sites. Blocking experiments confirmed the pivotal roles of Thy-1 on activated dermal EC or fibroblasts and its counter receptor CD18 on neutrophils for the regulation of MMP-9 and CXCL8 release from neutrophils. Our results support the general concept that the function of 'adhesion molecules' in particular of human Thy-1, may not only be to provide mechanical support but also regulate neutrophil functions.

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“…They are rapidly recruited in large numbers from the bloodstream by processes of adhesion to vascular endothelium, transendothelial migration, and chemotaxis to a local inflammatory site (2,3). In the presence of inflammatory mediators such as chemotactic agonists and cytokines (4), neutrophils interacting with plasma and extracellular matrix proteins (3,5,6) or endothelial counter-receptors reorganize their cytoskeleton and spread over the adhesive surface (7,8), diapedese, produce reactive oxygen intermediates, and release granule constituents (9 -13).…”

Section: Regulation Of Neutrophil Adhesion By Pituitary Growthmentioning

confidence: 99%

Regulation of Neutrophil Adhesion by Pituitary Growth Hormone Accompanies Tyrosine Phosphorylation of Jak2, p125FAK, and Paxillin

Ryu

Lee

Kim

et al. 2000

The Journal of Immunology

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Neutrophil adhesion is fundamentally important during the onset of inflammatory responses. The adhesion signaling pathways control neutrophil arrest and extravasation and influence neutrophil shape and function at sites of inflammation. In the present study the intracellular signaling pathways for the adhesion of human neutrophils by pituitary growth hormone (GH) were examined. Pituitary GH triggered the tyrosine phosphorylation of Janus kinase 2 (Jak2) and STAT3 in neutrophils. In addition, pituitary GH treatment resulted in the morphological changes and the tyrosine phosphorylation of focal adhesion kinase (p125FAK) and paxillin. Preincubation with genistein, a tyrosine kinase inhibitor, blocked the GH-stimulated adhesion and Jak2, STAT3, p125FAK, and paxillin phosphorylation. Confocal microscopy revealed that pituitary GH stimulates the focal localization of p125FAK, paxillin, phosphotyrosine, and filamentous actin filament into the membrane rufflings and uropods of human neutrophils. Immunoprecipitation experiments revealed a physical association of Jak2 with p125FAK via STAT3 in vivo. Also an in vitro kinase assay showed an augmentation of p125FAK autophosphorylation as a result of pituitary GH treatment. These results suggest that pituitary GH modulates neutrophil adhesion through tyrosine phosphorylation of Jak2, p125FAK, and paxillin and actin polymerization.

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β1 Integrins Are Critically Involved in Neutrophil Locomotion in Extravascular Tissue In Vivo

Cited by 144 publications

References 27 publications

Mesenchymal Stem Cells Use Integrin β1 Not CXC Chemokine Receptor 4 for Myocardial Migration and Engraftment

Mesenchymal Stem Cells Use Integrin β1 Not CXC Chemokine Receptor 4 for Myocardial Migration and Engraftment

Human Thy‐1 induces secretion of matrix metalloproteinase‐9 and CXCL8 from human neutrophils

Regulation of Neutrophil Adhesion by Pituitary Growth Hormone Accompanies Tyrosine Phosphorylation of Jak2, p125FAK, and Paxillin

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