S100B Regulates Pulmonary Neutrophil Recruitment In Lipopolysaccharide-induced Acute Lung Inflammation

The mechanisms of excessive migration of activated neutrophils into inflamed lungs, credited with tissue damage, are not fully understood. We explored the hitherto unknown expression of leukocyte-specific protein 1 (LSP1) in human and mouse lungs and neutrophils and examined its role in neutrophil migration in acute lung inflammation. Autopsied septic human lungs showed increased LSP1 labeling in epithelium, endothelium, and leukocytes, including in their nuclei compared with normal lungs. We induced acute lung inflammation through intranasal administration of E. coli lipopolysaccharide (LPS) (80 μg) in LSP1-deficient ( Lsp1−/−) and wild-type (WT) 129/SvJ mice. Immunocytochemistry and Western blots showed increased expression of LSP1 and phosphorylated LSP1 in lungs of LPS-treated WT mice. Histology showed more congestion, inflammation, and Gr-1+neutrophils in lung of WT mice than Lsp1−/−mice. LPS-treated WT mice had significantly more neutrophils in bronchoalveolar lavage (BAL) and myeloperoxidase levels in lungs compared with Lsp1−/−mice. However, there were no differences in lung tissue and BAL concentrations of keratinocyte-derived chemokine, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α and -1β, vascular permeability, and phosphorylated p38 MAPK between LPS-treated WT and Lsp1−/−mice, whereas TNF-α concentration was higher in BAL fluid from LPS-treated WT. Immunoelectron microscopy showed increased LSP1 in the nuclei of LPS-treated neutrophils. We also found increased levels of phosphorylated LSP1 associated with plasma membrane, nucleus, and cytosol at various times after LPS treatment of murine bone marrow-derived neutrophils, suggesting its role in modulation of neutrophil cytoskeleton and the membrane. These data collectively show increased expression of LSP1 in inflamed mouse and human lungs and its role in neutrophil recruitment and lung inflammation.

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Lack of CD34 delays bacterial endotoxin-induced lung inflammation

Respiratory Research ◽

10.1186/s12931-021-01667-2 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Gurpreet K. Aulakh ◽

Sushmita Maltare ◽

Baljit Singh

Keyword(s):

Lung Inflammation ◽

Neutrophil Migration ◽

Neutrophil Recruitment ◽

Multiple Time ◽

Acute Lung Inflammation ◽

Knock Out ◽

Time Points ◽

Bronchiolar Epithelium ◽

Alveolar Septa

Abstract Background CD34, a pan-selectin binding protein when glycosylated, has been shown to be involved in leukocyte migration to the site of inflammation. However, only one report is available on the expression and role of CD34 in neutrophil recruitment during acute lung inflammation. Methods We proceeded to study the role of CD34 in lung neutrophil migration using mouse model of endotoxin induced acute lung inflammation and studied over multiple time points, in generic CD34 knock-out (KO) strain. Results While there was no difference in BAL total or differential leukocyte counts, lung MPO content was lower in LPS exposed KO compared to WT group at 3 h time-point (p = 0.0308). The MPO levels in CD34 KO mice begin to rise at 9 h (p = 0.0021), as opposed to an early 3 h rise in WT mice (p = 0.0001), indicating that KO mice display delays in lung neutrophil recruitment kinetics. KO mice do not loose endotoxin induced lung vascular barrier properties as suggested by lower BAL total protein at 3 h (p = 0.0452) and 24 h (p = 0.0113) time-points. Several pro-inflammatory cytokines and chemokines (TNF-α, IL-1β, KC, MIP-1α, IL-6, IL-10 and IL-12 p70 sub-unit; p < 0.05) had higher levels in WT compared to KO group, at 3 h. Lung immunofluorescence in healthy WT mice reveals CD34 expression in the bronchiolar epithelium, in addition to alveolar septa. Conclusion Thus, given CD34′s pan-selectin affinity, and expression in the bronchiolar epithelium as well as alveolar septa, our study points towards a role of CD34 in lung neutrophil recruitment but not alveolar migration, cytokine expression and lung inflammation.

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Mannodendrimers prevent acute lung inflammation by inhibiting neutrophil recruitment

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1221708110 ◽

2013 ◽

Vol 110 (22) ◽

pp. 8795-8800 ◽

Cited By ~ 67

Author(s):

E. Blattes ◽

A. Vercellone ◽

H. Eutamene ◽

C.-O. Turrin ◽

V. Theodorou ◽

...

Keyword(s):

Lung Inflammation ◽

Neutrophil Recruitment ◽

Acute Lung Inflammation

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Siglec-E is a negative regulator of acute pulmonary neutrophil inflammation and suppresses CD11b β2-integrin–dependent signaling

Blood ◽

10.1182/blood-2012-08-449983 ◽

2013 ◽

Vol 121 (11) ◽

pp. 2084-2094 ◽

Cited By ~ 55

Author(s):

Sarah J. McMillan ◽

Ritu S. Sharma ◽

Emma J. McKenzie ◽

Hannah E. Richards ◽

Jiquan Zhang ◽

...

Keyword(s):

Lung Disease ◽

Lung Inflammation ◽

Potential Role ◽

Neutrophil Recruitment ◽

Negative Regulator ◽

Acute Lung Inflammation ◽

Inflammatory Lung Disease ◽

Β2 Integrin ◽

Key Points

Key Points First report describing in vivo function of siglec-E as a negative regulator of neutrophil recruitment in acute lung inflammation. Implications for the human functional ortholog, siglec-9, and its potential role in regulating inflammatory lung disease.

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STAT3-dependent CXC chemokine formation and neutrophil migration in streptococcal M1 protein-induced acute lung inflammation

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00324.2014 ◽

2015 ◽

Vol 308 (11) ◽

pp. L1159-L1167 ◽

Cited By ~ 8

Author(s):

Songen Zhang ◽

Rundk Hwaiz ◽

Lingtao Luo ◽

Heiko Herwald ◽

Henrik Thorlacius

Keyword(s):

Streptococcus Pyogenes ◽

Lung Inflammation ◽

Neutrophil Migration ◽

Neutrophil Recruitment ◽

Acute Lung Inflammation ◽

Chemokine Production ◽

Stat3 Signaling ◽

M1 Protein ◽

Cxc Chemokine

Streptococcus pyogenes cause infections ranging from mild pharyngitis to severe streptococcal toxic shock syndrome (STSS). The M1 serotype of Streptococcus pyogenes is most frequently associated with STSS. Herein, it was hypothesized that STAT3 signaling might be involved in M1 protein-evoked lung inflammation. The STAT3 inhibitor, S3I-201, was administered to male C57Bl/6 mice before iv challenge with M1 protein. Bronchoalveolar fluid and lung tissue were harvested for quantification of STAT3 activity, neutrophil recruitment, edema, and CXC chemokine formation. Neutrophil expression of Mac-1 was quantified by use of flow cytometry. Levels of IL-6 and HMGB1 were determined in plasma. CXCL2-induced neutrophil chemotaxis was studied in vitro. Administration of S3I-201 markedly reduced M1 protein-provoked STAT3 activity, neutrophil recruitment, edema formation, and inflammatory changes in the lung. In addition, M1 protein significantly increased Mac-1 expression on neutrophils and CXC chemokine levels in the lung. Treatment with S3I-201 had no effect on M1 protein-induced expression of Mac-1 on neutrophils. In contrast, inhibition of STAT3 activity greatly reduced M1 protein-induced formation of CXC chemokines in the lung. Interestingly, STAT3 inhibition markedly decreased plasma levels of IL-6 and HMGB1 in animals exposed to M1 protein. Moreover, we found that S3I-201 abolished CXCL2-induced neutrophil migration in vitro. In conclusion, these novel findings indicate that STAT3 signaling plays a key role in mediating CXC chemokine production and neutrophil infiltration in M1 protein-induced acute lung inflammation.

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Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon Dots

Nanomaterials ◽

10.3390/nano11010180 ◽

2021 ◽

Vol 11 (1) ◽

pp. 180

Author(s):

Maud Weiss ◽

Jiahui Fan ◽

Mickaël Claudel ◽

Luc Lebeau ◽

Françoise Pons ◽

...

Keyword(s):

Carbon Dots ◽

Lung Inflammation ◽

Adverse Outcome ◽

Cellular Responses ◽

Target Cells ◽

Inflammasome Activation ◽

Adverse Outcome Pathway ◽

Acute Lung Inflammation

With the growth of nanotechnologies, concerns raised regarding the potential adverse effects of nanoparticles (NPs), especially on the respiratory tract. Adverse outcome pathways (AOP) have become recently the subject of intensive studies in order to get a better understanding of the mechanisms of NP toxicity, and hence hopefully predict the health risks associated with NP exposure. Herein, we propose a putative AOP for the lung toxicity of NPs using emerging nanomaterials called carbon dots (CDs), and in vivo and in vitro experimental approaches. We first investigated the effect of a single administration of CDs on mouse airways. We showed that CDs induce an acute lung inflammation and identified airway macrophages as target cells of CDs. Then, we studied the cellular responses induced by CDs in an in vitro model of macrophages. We observed that CDs are internalized by these cells (molecular initial event) and induce a series of key events, including loss of lysosomal integrity and mitochondrial disruption (organelle responses), as well as oxidative stress, inflammasome activation, inflammatory cytokine upregulation and macrophage death (cellular responses). All these effects triggering lung inflammation as tissular response may lead to acute lung injury.

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