Elevated CXCL1 expression in gp130-deficient endothelial cells impairs neutrophil migration in mice

Yao, Longbiao; Yago, Tadayuki; Shao, Bojing; Liu, Zhenghui; Silasi‐Mansat, Robert; Setiadi, Hendra; Lupu, Florea; McEver, Rodger P.

doi:10.1182/blood-2012-12-473835

Cited by 33 publications

(41 citation statements)

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“…39 Previous models of TNF-or thioglycollate-induced inflammation may have overestimated the ability of PTx to block chemokine signaling in endogenous neutrophils for prolonged periods. 11,27,28,37,39,41,45,49 This could explain why some signaling pathways attributed to selectins, notably activation of PI3Kg, could instead be caused by chemokines. Although we cannot exclude some contribution of selectins to activating PI3Kg in neutrophils, our data indicate that chemokine-induced signals are dominant.…”

Section: Discussionmentioning

confidence: 99%

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Selectins and chemokines use shared and distinct signals to activate β2 integrins in neutrophils

et al. 2018

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Section: Discussionmentioning

confidence: 99%

“…In some experiments, mouse neutrophils were isolated from bone marrow leukocytes by a density gradient method. 37 …”

Section: Cellsmentioning

confidence: 99%

Selectins and chemokines use shared and distinct signals to activate β2 integrins in neutrophils

et al. 2018

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“…As CXCR2 ligands were particularly downregulated in airway epithelium, we investigated whether recombinant CXCL1, CXCL2, or CXCL5 could rescue impaired bacterial clearance in the ethanol group. Local delivery of recombinant CXCL1 and CXCL5 (doses used in previous studies [16][17][18]) but not CXCL2 significantly decreased bacterial burden compared to the ethanol group that received vehicle control (Fig. 6C).…”

Section: (Paired T Test) (B) Gene Expression Data From Panelmentioning

confidence: 98%

Ethanol Impairs Mucosal Immunity against Streptococcus pneumoniae Infection by Disrupting Interleukin 17 Gene Expression

et al. 2015

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Acute ethanol intoxication suppresses the host immune responses against Streptococcus pneumoniae. As interleukin 17 (IL-17) is a critical cytokine in host defense against extracellular pathogens, including S. pneumoniae, we hypothesized that ethanol impairs mucosal immunity against this pathogen by disrupting IL-17 production or IL-17 receptor (IL-17R) signaling. A chronic ethanol feeding model in simian immunodeficiency virus (SIV)-infected rhesus macaques and acute ethanol intoxication in a murine model were used. Transcriptome analysis of bronchial brushes in the nonhuman primate model showed downregulation of the expression of IL-17-regulated chemokines in ethanol-fed animals, a finding also replicated in the murine model. Surprisingly, recombinant CXCL1 and CXCL5 but not IL-17 or IL-23 plus IL-1␤ rescued bacterial burden in the ethanol group to control levels. Taken together, the results of this study suggest that ethanol impairs IL-17-mediated chemokine production in the lung. Thus, exogenous luminal restoration of IL-17-related chemokines, CXCL1 and CXCL5, improves host defenses against S. pneumoniae. Bacterial pneumonia is a complication of ethanol abuse, and this susceptibility was documented both in animal models and in human studies more than a century ago (1, 2). Excessive ethanol consumption remains a public health problem responsible for approximately 79,000 deaths in the United States each year and for an estimated economic cost of $223.5 billion in 2006 (3).Streptococcus pneumoniae is a Gram-positive bacterium and the leading etiology of community-acquired pneumonia, especially in older adults and alcoholic patients. Innate immune responses are important to control infections by S. pneumoniae, as evidenced by the roles of Toll-like receptors, MyD88, and IRAK4 in both humans and animal models (4, 5). More recently, evidence has emerged to support the fact that interleukin 17 (IL-17) plays a critical role in the regulation of S. pneumoniae colonization and infection. IL-17 and CD4 ϩ T cells, and specifically the Th17 subset, are important for clearance of nasopharyngeal colonization with S. pneumoniae (a prerequisite of pneumococcal pneumonia) during primary and secondary infection (6, 7).IL-17 is a cytokine produced by activated CD4 ϩ T cells and innate lymphocytes (␥␦ ϩ T cells, NK cells, and innate lymphoid cells) and drives inflammation and autoimmunity (8). In the lung, the airway epithelium plays an important role in orchestrating the production of C-X-C chemokines, and these cells express both IL-17RA and IL-17RC and can produce both C-X-C chemokines and granulocyte colony-stimulating factor (G-CSF) in response to IL-17, leading to neutrophil recruitment in vivo (9-11).As the lung epithelium is a major site of chemokine production during bacterial pneumonia (12), we examined the effect of ethanol on gene expression in the airway epithelium during experimental S. pneumoniae infection in a nonhuman primate model of ethanol consumption and pneumococcal infection (13,14). We analyzed bronchial b...

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“…The enriched HS GAGs might be necessary to maintain functional chemokine gradients toward the basolateral aspects of blood vessels. Indeed, excess deposition of the HS binding chemokine CXCL1 on apical aspects of inflamed blood vessels results in reduced neutrophil diapedesis (Yao et al, 2013). Of note, HS or other GAGs do not appear to be essential for all types of inflammatory reactions…”

Section: Exit Cues For Leukocyte Transmigrationmentioning

confidence: 99%

Leukocyte Migration into Inflamed Tissues

2014

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Leukocyte migration through activated venular walls is a fundamental immune response that is prerequisite to the entry of effector cells such as neutrophils, monocytes, and effector T cells to sites of infection, injury, and stress within the interstitium. Stimulation of leukocytes is instrumental in this process with enhanced temporally controlled leukocyte adhesiveness and shape-changes promoting leukocyte attachment to the inner wall of blood vessels under hydrodynamic forces. This initiates polarized motility of leukocytes within and through venular walls and transient barrier disruption facilitated sequentially by stimulated vascular cells, i.e., endothelial cells and their associated pericytes. Perivascular cells such as macrophages and mast cells that act as tissue inflammatory sentinels can also directly and indirectly regulate the exit of leukocytes from the vascular lumen. In this review, we discuss current knowledge and open questions regarding the mechanisms involved in the interactions of different effector leukocytes with peripheral vessels in extralymphoid organs.

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Elevated CXCL1 expression in gp130-deficient endothelial cells impairs neutrophil migration in mice

Abstract: Key Points Elevated CXCL1 expression on gp130-deficient endothelial cells triggers neutrophil arrest but impairs transendothelial migration. Loss of endothelial cell gp130 dysregulates integrin-dependent adhesion and de-adhesion of neutrophils during inflammation.

Cited by 33 publications

References 50 publications

Selectins and chemokines use shared and distinct signals to activate β2 integrins in neutrophils

Selectins and chemokines use shared and distinct signals to activate β2 integrins in neutrophils

Ethanol Impairs Mucosal Immunity against Streptococcus pneumoniae Infection by Disrupting Interleukin 17 Gene Expression

Leukocyte Migration into Inflamed Tissues

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