Blocking p21-activated Kinase Reduces Lipopolysaccharide-induced Acute Lung Injury by Preventing Polymorphonuclear Leukocyte Infiltration

Reutershan, Jörg; Stockton, Rebecca; Zarbock, Alexander; Sullivan, Gail W.; Chang, Daniel H.; Scott, David A.; Schwartz, Martin A.; Ley, Klaus

doi:10.1164/rccm.200612-1822oc

Cited by 41 publications

(49 citation statements)

References 48 publications

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“…PAK1/ p21protein (Cdc42/Rac)-activated kinase 1 is known for taking part in the regulation of chemotaxis, chemokin-indused cytoskeletal actin polymerization, and oxidative burst. 34,35 We found that the expression of S100A8, a recently described proinflammatory protein expressed by phagocytes and implicated both in NADPH oxidase activation by interaction with NCF2/p67PHOX or transepithelial migration of neutrophils also remained at lower level in TG2-KD NB4 cells. 36,37 These examples suggest that TG2 is required for the development of the full innate immune function of differentiating NB4 cells including their full inflammatory responsiveness ( Figure 5C-F).…”

Section: Tg2 Strengthens the Development Of Ds 3941mentioning

confidence: 77%

Tissue transglutaminase contributes to the all-trans-retinoic acid–induced differentiation syndrome phenotype in the NB4 model of acute promyelocytic leukemia

Csomós

Német

Fésüs

et al. 2010

Blood

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Section: Tg2 Strengthens the Development Of Ds 3941mentioning

confidence: 77%

Tissue transglutaminase contributes to the all-trans-retinoic acid–induced differentiation syndrome phenotype in the NB4 model of acute promyelocytic leukemia

Csomós

Német

Fésüs

et al. 2010

Blood

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“…LPS-induced expression of A1AR protein in whole lung tissue was evaluated by Western blotting as previously described (15). Briefly, lungs were snap frozen and lysed in RIPA buffer [1% Nonidet P-40, 1% deoxycholate, 0.1% SDS, 50 mM Tris (pH 7.4), 150 mM NaCl, protease, and phosphatase I and II inhibitors].…”

Section: Western Blottingmentioning

confidence: 99%

“…Besides adhesion molecules (13), chemokines (14), and intracellular molecules (15), extracellular adenosine is an essential mediator of leukocyte trafficking to inflammatory sites. Adenosine signals through four subtypes of G protein-coupled adenosine receptors (ARs; A1, A2a, A2b, and A3) that are ubiquitary expressed on various hematopoietic and nonhematopoietic cells.…”

mentioning

confidence: 99%

Adenosine Receptor A1 Regulates Polymorphonuclear Cell Trafficking and Microvascular Permeability in Lipopolysaccharide-Induced Lung Injury

Ngamsri

Wagner

Vollmer

et al. 2010

The Journal of Immunology

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Extracellular adenosine and adenosine receptors are critically involved in various inflammatory pathways. Adenosine receptor A1 (A1AR) has been implicated in mediating transmigration of leukocytes to sites of inflammation. This study was designed to characterize the role of A1AR in a murine model of LPS-induced lung injury. LPS-induced transmigration of polymorphonuclear cells (PMNs) and microvascular permeability was elevated in A1AR−/− mice. Pretreatment of wild-type mice with the specific A1AR agonist 2′Me–2-chloro-N6-cyclopentyladenosine attenuated PMN accumulation in the interstitium and alveolar space as well as microvascular permeability. Lower PMN counts in the lungs of pretreated wild-type mice were associated with reduced amounts of the chemotactic cytokines TNF-α, IL-6, and CXCL2/3 in the bronchoalveolar lavage. Pretreatment was only effective when A1AR was expressed on hematopoietic cells as demonstrated in chimeric mice. These findings were confirmed by in vitro transmigration assays demonstrating that chemokine-induced transmigration of PMNs was reduced when PMNs but not when pulmonary endothelial or alveolar epithelial cells were pretreated. 2′Me–2-chloro-N6-cyclopentyladenosine prevented pulmonary endothelial but not epithelial cells from LPS-induced cellular remodeling and cell retraction. Our data reveal what we believe to be a previously unrecognized distinct role of A1AR for PMN trafficking and endothelial integrity in a model of acute lung injury.

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“…As described previously, 33 LPS from Salmonella enteritidis (500 g/mL; Sigma-Aldrich, St Louis, MO) was nebulized to induce pulmonary inflammation. Briefly, mice were exposed 30 minutes to aerosolized LPS or saline aerosol as a control.…”

Section: Murine Model Of Lps-induced Pulmonary Inflammationmentioning

confidence: 99%

Gαi2 is required for chemokine-induced neutrophil arrest

Zarbock

Deem

Burcin

et al. 2007

Blood

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Chemokines, including CXCL1, participate in neutrophil recruitment by triggering the activation of integrins, which leads to arrest from rolling. The downstream signaling pathways which lead to integrin activation and neutophil arrest following G-protein-coupled receptor engagement are incompletely understood. To test whether G␣ i2 is involved, mouse neutrophils in their native whole blood were investigated in mouse cremaster postcapillary venules and in flow chambers coated with P-selectin, ICAM-1, and CXCL1. Gnai2 Ϫ/Ϫ neutrophils showed significantly reduced CXCL1-induced arrest in vitro and in vivo. Similar results were obtained with leukotriene B 4 (LTB 4 ). Lethally irradiated mice reconstituted with Gnai2 Ϫ/Ϫ bone marrow showed a similar defect in chemoattractant-induced arrest as that of Gnai2 Ϫ/Ϫ mice. In thioglycollate-induced peritonitis and lipopolysaccaride (LPS)-induced lung inflammation, chimeric mice lacking G␣ i2 in hematopoietic cells showed about 50% reduced neutrophil recruitment similar to that seen in Gnai2 Ϫ/Ϫ mice. These data show that neutrophil G␣ i2 is necessary for chemokineinduced arrest, which is relevant for neutrophil recruitment to sites of acute inflammation.(Blood.

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Blocking p21-activated Kinase Reduces Lipopolysaccharide-induced Acute Lung Injury by Preventing Polymorphonuclear Leukocyte Infiltration

Cited by 41 publications

References 48 publications

Tissue transglutaminase contributes to the all-trans-retinoic acid–induced differentiation syndrome phenotype in the NB4 model of acute promyelocytic leukemia

Tissue transglutaminase contributes to the all-trans-retinoic acid–induced differentiation syndrome phenotype in the NB4 model of acute promyelocytic leukemia

Adenosine Receptor A1 Regulates Polymorphonuclear Cell Trafficking and Microvascular Permeability in Lipopolysaccharide-Induced Lung Injury

Gαi2 is required for chemokine-induced neutrophil arrest

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