Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury

Block, Helena; Herter, Jan M.; Rossaint, Jan; Stadtmann, Anika; Kliche, Stefanie; Lowell, Clifford A.; Zarbock, Alexander

doi:10.1084/jem.20111493

Cited by 87 publications

(118 citation statements)

References 73 publications

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“…This step is defective in mice lacking either the Src kinase Fgr or both Hck and Lyn (19): neutrophils from these mice fail to consecutively phosphorylate the spleen tyrosine kinase (Syk) (19). Syk activates a protein complex of the Src homology 2 domaincontaining leukocyte phosphoprotein of 76 kDa (SLP76) and the adhesion and degranulation-promoting adaptor protein (ADAP) (20). SLP76, in turn, activates Bruton tyrosine kinase (20).…”

Section: Leukocyte Recruitmentmentioning

confidence: 99%

“…Syk activates a protein complex of the Src homology 2 domaincontaining leukocyte phosphoprotein of 76 kDa (SLP76) and the adhesion and degranulation-promoting adaptor protein (ADAP) (20). SLP76, in turn, activates Bruton tyrosine kinase (20). Both Bruton tyrosine kinase and ADAP are needed to signal downstream via two independent branches (20): one is phospholipase C (PLC)g2 dependent and comprises Calcium diacylglycerol guanine nucleotide exchange factor I (CalDAG-GEFI), p38 MAPK, and Rap1a (21).…”

Section: Leukocyte Recruitmentmentioning

confidence: 99%

“…SLP76, in turn, activates Bruton tyrosine kinase (20). Both Bruton tyrosine kinase and ADAP are needed to signal downstream via two independent branches (20): one is phospholipase C (PLC)g2 dependent and comprises Calcium diacylglycerol guanine nucleotide exchange factor I (CalDAG-GEFI), p38 MAPK, and Rap1a (21). The other pathway is PI3Kg dependent (22).…”

Section: Leukocyte Recruitmentmentioning

confidence: 99%

“…In the following text we discuss mechanisms that physiologically regulate leukocyte integrin activation at the site of inflammation. Impairment of these local responses may cause constitutive integrin activation leading to autoimmune diseases, unnecessary tissue damage, and deterioration of organ function (20). Mechanisms that limit leukocyte recruitment by regulating the activation of integrins were identified at several cellular levels (Fig, 1B) This effect is partially mediated by a pronounced decrease in the expression of PSGL-1, CD11b (Mac-1), and L-selectin on the cell surface of neutrophils (66).…”

Section: Integrin Regulation At the Site Of Inflammationmentioning

confidence: 99%

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Integrin Regulation during Leukocyte Recruitment

Herter

Zarbock

2013

The Journal of Immunology

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169

138

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Integrins are recognized as vital players in leukocyte recruitment. Integrin malfunction causes severe disease patterns characterized by the inability to fight pathogens. Although inflammatory reactions are beneficial and necessary for host defense, these reactions have to be controlled to prevent tissue destruction and harmful sequelae. In this review, we discuss the different signaling pathways leading to the change of integrin adhesiveness in neutrophils, monocytes, and lymphocytes. We thereby focus on the importance of integrin activation for the different steps of the leukocyte recruitment cascade, including rolling, adhesion, postadhesion strengthening, intravascular crawling, and transmigration, as each step necessitates the proper functioning of a distinct set of integrin molecules that has to be activated specifically. Additionally, we discuss endogenous mechanisms that balance and counteract integrin activation and limit leukocyte recruitment at the site of inflammation. Further insight into these complex mechanisms may provide new approaches for developing new anti-inflammatory therapies.

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Section: Leukocyte Recruitmentmentioning

confidence: 99%

Section: Leukocyte Recruitmentmentioning

confidence: 99%

Section: Leukocyte Recruitmentmentioning

confidence: 99%

Section: Integrin Regulation At the Site Of Inflammationmentioning

confidence: 99%

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Integrin Regulation during Leukocyte Recruitment

Herter

Zarbock

2013

The Journal of Immunology

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169

138

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“…In platelets, loss of ADAP results in impaired a IIb b 3 integrin activation, leading to increased rebleeding of ADAPdeficient mice from tail wounds (20) and to instable thrombus formation after carotid artery injury in vivo (21). Recently, it was shown that loss of ADAP attenuated neutrophil recruitment in an ischemia-reperfusion-induced acute kidney injury model (22).…”

mentioning

confidence: 99%

T Cell–Independent Modulation of Experimental Autoimmune Encephalomyelitis in ADAP-Deficient Mice

Engelmann

Togni

Thielitz

et al. 2013

The Journal of Immunology

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The adhesion- and degranulation-promoting adaptor protein (ADAP), expressed in T cells, myeloid cells, and platelets, is known to regulate receptor-mediated inside-out signaling leading to integrin activation and adhesion. In this study, we demonstrate that, upon induction of active experimental autoimmune encephalomyelitis (EAE) by immunization with the myelin oligodendrocyte glycoprotein35–55 peptide, ADAP-deficient mice developed a significantly milder clinical course of EAE and showed markedly less inflammatory infiltrates in the CNS than wild-type mice. Moreover, ADAP-deficient recipients failed to induce EAE after adoptive transfer of myelin oligodendrocyte glycoprotein–specific TCR-transgenic T cells (2D2 T cells). In addition, ex vivo fully activated 2D2 T cells induced significantly less severe EAE in ADAP-deficient recipients. The ameliorated disease in the absence of ADAP was not due to expansion or deletion of a particular T cell subset but rather because of a strong reduction of all inflammatory leukocyte populations invading the CNS. Monitoring the adoptively transferred 2D2 T cells over time demonstrated that they accumulated within the lymph nodes of ADAP-deficient hosts. Importantly, transfer of complete wild-type bone marrow or even bone marrow of 2D2 TCR–transgenic mice was unable to reconstitute EAE in the ADAP-deficient animals, indicating that the milder EAE was dependent on (a) radio-resistant nonhematopoietic cell population(s). Two-photon microscopy of lymph node explants revealed that adoptively transferred lymphocytes accumulated at lymphatic vessels in the lymph nodes of ADAP-deficient mice. Thus, our data identify a T cell–independent mechanism of EAE modulation in ADAP-deficient mice.

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SLP‐76 is required for optimal CXCR4‐stimulated T lymphocyte firm arrest to ICAM‐1 under shear flow

et al. 2012

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Summary Rapid arrest of T cells at target sites upon engagement of chemokine receptors is crucial to the proper functioning of the immune system. Although T cell arrest always occurs under hydrodynamic forces in vivo, most studies investigating the molecular mechanisms of arrest have been performed under static conditions. While the requirement of the adaptor protein SLP-76 in TCR-induced integrin activation has been demonstrated, its role in chemokine-triggered T cell adhesion is unknown. Using a flow chamber system, we show that SLP-76 plays an important role in regulating the transition from tethering and rolling to firm adhesion of T cells under physiological shear flow in response to CXCL12α SDF-1α); SLP-76-deficient primary T cells exhibited defective adhesion with a significant decrease in the number of firmly arrested cells. We further demonstrate the N-terminal phosphotyrosines of SLP-76 play a critical role in this T cell adhesion under flow. These findings reveal a novel role for SLP-76 in CXCR4-mediated T lymphocyte trafficking.

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Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury

Abstract: Leukocyte recruitment to the kidney during acute injury is mediated by E-selectin–mediated rolling and requires SLP-76 and the adaptor protein ADAP.

Cited by 87 publications

References 73 publications

Integrin Regulation during Leukocyte Recruitment

Integrin Regulation during Leukocyte Recruitment

T Cell–Independent Modulation of Experimental Autoimmune Encephalomyelitis in ADAP-Deficient Mice

SLP‐76 is required for optimal CXCR4‐stimulated T lymphocyte firm arrest to ICAM‐1 under shear flow

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