scholarly journals Leukocyte-specific protein 1 regulates neutrophil recruitment in acute lung inflammation

2015 ◽  
Vol 309 (9) ◽  
pp. L995-L1008 ◽  
Author(s):  
Nguyen Phuong Khanh Le ◽  
Shankaramurthy Channabasappa ◽  
Mokarram Hossain ◽  
Lixin Liu ◽  
Baljit Singh
Keyword(s):  
Lung Inflammation ◽  
Neutrophil Migration ◽  
Specific Protein ◽  
Neutrophil Recruitment ◽  
Acute Lung Inflammation ◽  
Western Blots ◽  
Monocyte Chemoattractant Protein 1 ◽  
Murine Bone Marrow ◽  
Human Lungs ◽  
Activated Neutrophils

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.

scholarly journals Lack of CD34 delays bacterial endotoxin-induced lung inflammation

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.

scholarly journals Leukocyte‐Specific Protein 1 (LSP1) regulates neutrophil migration in acute lung inflammation

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Phuong Khanh Le Nguyen ◽  
Shankaramurthy Channabasappa ◽  
Lixin Liu ◽  
Baljit Singh
Keyword(s):  
Lung Inflammation ◽  
Neutrophil Migration ◽  
Specific Protein ◽  
Acute Lung Inflammation

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

2015 ◽  
Vol 308 (11) ◽  
pp. L1159-L1167 ◽  
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.

scholarly journals Pulmonary Endothelial Protein Kinase C-Delta (PKCδ) Regulates Neutrophil Migration in Acute Lung Inflammation

2014 ◽  
Vol 184 (1) ◽  
pp. 200-213 ◽  
Author(s):  
Mark J. Mondrinos ◽  
Ting Zhang ◽  
Shuang Sun ◽  
Paul A. Kennedy ◽  
Devon J. King ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Lung Inflammation ◽  
Neutrophil Migration ◽  
Acute Lung Inflammation ◽  
Protein Kinase C Delta ◽  
Kinase C

scholarly journals Clara Cell Specific Protein (CC16) Expression after Acute Lung Inflammation Induced by Intratracheal Lipopolysaccharide Administration

2000 ◽  
Vol 161 (5) ◽  
pp. 1624-1630 ◽  
Author(s):  
KARIM ARSALANE ◽  
FABRICE BROECKAERT ◽  
BERNARD KNOOPS ◽  
MURIELLE WIEDIG ◽  
GERARD TOUBEAU ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Specific Protein ◽  
Clara Cell ◽  
Acute Lung Inflammation

scholarly journals A peptide derived from chaperonin 60.1, IRL201104, inhibits LPS-induced acute lung inflammation

2021 ◽  
Author(s):  
Francis Man ◽  
Suchita Nadkarni ◽  
Varsha Kanabar ◽  
Rodrigo e-Lacerda ◽  
Sueli Gomes Ferreira ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Lung Inflammation ◽  
Umbilical Vein ◽  
Neutrophil Migration ◽  
Human Neutrophils ◽  
Integrin Expression ◽  
Annexin A1 ◽  
Adhesion Molecule Expression ◽  
Acute Lung Inflammation ◽  
Anti Inflammatory

Chaperonin 60.1 (Cpn60.1) is a protein derived from M. tuberculosis that has been shown, along with its peptide fragment IRL201104, to have beneficial effects in models of allergic inflammation. To further investigate the anti-inflammatory properties of Cpn60.1 and IRL201104, we have investigated these molecules in a model of non-allergic lung inflammation. Mice were treated with Cpn60.1 (0.5-5000ng/kg) or IRL201104 (0.00025-2.5ng/kg), immediately before intranasal instillation of bacterial lipopolysaccharide (LPS). Cytokine levels and cell numbers in mouse bronchoalveolar lavage (BAL) fluid were measured 4h after LPS administration. In some experiments mice were depleted of lung-resident phagocytes. Cells from BAL fluid were analysed for inflammasome function. Human umbilical vein endothelial cells (HUVEC) were analysed for adhesion molecule expression. Human neutrophils were analysed for integrin expression, chemotaxis and cell polarisation. Cpn60.1 and IRL201104 significantly inhibited neutrophil migration into the airways, independently of route of administration. This effect of the peptide was absent in TLR4 and Annexin A1 knock-out mice. Intravital microscopy revealed that IRL201104 reduced leukocyte adhesion and migration into inflamed tissues. However, IRL201104 did not significantly affect adhesion molecule expression in HUVEC or integrin expression, chemotaxis or polarisation of human neutrophils at the studied concentrations. In phagocyte-depleted animals, the anti-inflammatory effect of IRL201104 was not significant. IRL201104 significantly reduced IL-1β and NLRP3 expression and increased A20 expression in BAL cells. This study shows that Cpn60.1 and IRL201104 potently inhibit LPS-induced neutrophil infiltration in mouse lungs by a mechanism dependent on tissue-resident phagocytes and to a much lesser extent the pro-resolving factor Annexin A1.

scholarly journals Mannodendrimers prevent acute lung inflammation by inhibiting neutrophil recruitment

2013 ◽  
Vol 110 (22) ◽  
pp. 8795-8800 ◽  
Author(s):  
E. Blattes ◽  
A. Vercellone ◽  
H. Eutamene ◽  
C.-O. Turrin ◽  
V. Theodorou ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Neutrophil Recruitment ◽  
Acute Lung Inflammation

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

Blood ◽  
2013 ◽  
Vol 121 (11) ◽  
pp. 2084-2094 ◽  
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.

scholarly journals Supramolecular Organization Predicts Protein Nanoparticle Delivery to Neutrophils for Acute Lung Inflammation Diagnosis and Treatment

2020 ◽  
Author(s):  
Jacob W. Myerson ◽  
Priyal N. Patel ◽  
Nahal Habibi ◽  
Landis R. Walsh ◽  
Yi-Wei Lee ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Ex Vivo ◽  
Supramolecular Organization ◽  
Acute Lung Inflammation ◽  
Viral Capsids ◽  
Nanoparticle Delivery ◽  
Pulmonary Capillaries ◽  
Human Lungs ◽  
Neutrophil Extravasation

AbstractAcute lung inflammation has severe morbidity, as seen in COVID-19 patients. Lung inflammation is accompanied or led by massive accumulation of neutrophils in pulmonary capillaries (“margination”). We sought to identify nanostructural properties that predispose nanoparticles to accumulate in pulmonary marginated neutrophils, and therefore to target severely inflamed lungs. We designed a library of nanoparticles and conducted an in vivo screen of biodistributions in naive mice and mice treated with lipopolysaccharides. We found that supramolecular organization of protein in nanoparticles predicts uptake in inflamed lungs. Specifically, nanoparticles with agglutinated protein (NAPs) efficiently home to pulmonary neutrophils, while protein nanoparticles with symmetric structure (e.g. viral capsids) are ignored by pulmonary neutrophils. We validated this finding by engineering protein-conjugated liposomes that recapitulate NAP targeting to neutrophils in inflamed lungs. We show that NAPs can diagnose acute lung injury in SPECT imaging and that NAP-like liposomes can mitigate neutrophil extravasation and pulmonary edema arising in lung inflammation. Finally, we demonstrate that ischemic ex vivo human lungs selectively take up NAPs, illustrating translational potential. This work demonstrates that structure-dependent interactions with neutrophils can dramatically alter the biodistribution of nanoparticles, and NAPs have significant potential in detecting and treating respiratory conditions arising from injury or infections.

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