Role of resident alveolar macrophages in leukocyte traffic into the alveolar air space of intact mice

2002 ◽  
Vol 282 (6) ◽  
pp. L1245-L1252 ◽  
Author(s):  
Ulrich a. Maus ◽  
M. Audrey Koay ◽  
Tim Delbeck ◽  
Matthias Mack ◽  
Monika Ermert ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Lung Inflammation ◽  
Intratracheal Instillation ◽  
Acute Lung Inflammation ◽  
Monocyte Chemoattractant ◽  
Lps Challenge ◽  
Inflammatory Conditions ◽  
Monocyte Recruitment ◽  
Lps Treatment

Intratracheal instillation of the monocyte chemoattractant JE/monocyte chemoattractant protein (MCP)-1 in mice was recently shown to cause increased alveolar monocyte accumulation in the absence of lung inflammation, whereas combined JE/MCP-1/lipopolysaccharide (LPS) challenge provoked acute lung inflammation with early alveolar neutrophil and delayed alveolar monocyte influx. We evaluated the role of resident alveolar macrophages (rAM) in these leukocyte recruitment events and related phenomena of lung inflammation. Depletion of rAM by pretreatment of mice with liposomal clodronate did not affect the JE/MCP-1-driven alveolar monocyte accumulation, despite the observation that rAM constitutively expressed the JE/MCP-1 receptor CCR2, as analyzed by flow cytometry and immunohistochemistry. In contrast, depletion of rAM largely suppressed alveolar cytokine release as well as neutrophil and monocyte recruitment profiles upon combined JE/MCP-1/LPS treatment. Despite this strongly attenuated alveolar inflammatory response, increased lung permeability was still observed in rAM-depleted mice undergoing JE/MCP-1/LPS challenge. Lung leakage was abrogated by codepletion of circulating neutrophils or administration of anti-CD18. Collectively, rAM are not involved in JE/MCP-1-driven alveolar monocyte recruitment in noninflamed lungs but largely contribute to the alveolar cytokine response and enhanced early neutrophil and delayed monocyte influx under inflammatory conditions (JE/MCP-1/LPS deposition). Loss of lung barrier function observed under these conditions is rAM independent but involves circulating neutrophils via β2-integrin engagement.

scholarly journals BPIFA1 regulates lung neutrophil recruitment and interferon signaling during acute inflammation

2019 ◽  
Vol 316 (2) ◽  
pp. L321-L333 ◽  
Author(s):  
Clemente J. Britto ◽  
Naiqian Niu ◽  
Sara Khanal ◽  
Luai Huleihel ◽  
Jose D. Herazo-Maya ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Acute Inflammation ◽  
Biological Significance ◽  
Polymorphonuclear Cells ◽  
Interferon Signaling ◽  
Acute Lung Inflammation ◽  
Chemokine Ligand ◽  
Group A ◽  
Lps Treatment

Bpifa1 (BPI fold-containing group A member 1) is an airway host-protective protein with immunomodulatory properties that binds to LPS and is regulated by infectious and inflammatory signals. Differential expression of Bpifa1 has been widely reported in lung disease, yet the biological significance of this observation is unclear. We sought to understand the role of Bpifa1 fluctuations in modulating lung inflammation. We treated wild-type (WT) and Bpifa1−/− mice with intranasal LPS and performed immunological and transcriptomic analyses of lung tissue to determine the immune effects of Bpifa1 deficiency. We show that neutrophil (polymorphonuclear cells, PMNs) lung recruitment and transmigration to the airways in response to LPS is impaired in Bpifa1−/− mice. Transcriptomic analysis revealed a signature of 379 genes that differentiated Bpifa1−/− from WT mice. During acute lung inflammation, the most downregulated genes in Bpifa1−/− mice were Cxcl9 and Cxcl10. Bpifa1−/− mice had lower bronchoalveolar lavage concentrations of C-X-C motif chemokine ligand 10 (Cxcl10) and Cxcl9, interferon-inducible PMN chemokines. This was consistent with lower expression of IFNγ, IFNλ, downstream IFN-stimulated genes, and IFN-regulatory factors, which are important for the innate immune response. Administration of Cxcl10 before LPS treatment restored the inflammatory response in Bpifa1−/− mice. Our results identify a novel role for Bpifa1 in the regulation of Cxcl10-mediated PMN recruitment to the lungs via IFNγ and -λ signaling during acute inflammation.

scholarly journals Induction of acute lung inflammation in mice with hemorrhagic shock and resuscitation: role of HMGB1

2014 ◽  
Vol 11 (1) ◽  
Author(s):  
Raymond LC Kao ◽  
Xuemei Xu ◽  
Anargyros Xenocostas ◽  
Neil Parry ◽  
Tina Mele ◽  
...  
Keyword(s):  
Hemorrhagic Shock ◽  
Lung Inflammation ◽  
Acute Lung Inflammation

scholarly journals Role of CD14 in a Mouse Model of Acute Lung Inflammation Induced by Different Lipopolysaccharide Chemotypes

PLoS ONE ◽  
2010 ◽  
Vol 5 (4) ◽  
pp. e10183 ◽  
Author(s):  
Adam A. Anas ◽  
Joppe W. R. Hovius ◽  
Cornelis van 't Veer ◽  
Tom van der Poll ◽  
Alex F. de Vos
Keyword(s):  
Mouse Model ◽  
Lung Inflammation ◽  
Acute Lung Inflammation

scholarly journals Anti-inflammatory role of PGD2 in acute lung inflammation and therapeutic application of its signal enhancement

2013 ◽  
Vol 110 (13) ◽  
pp. 5205-5210 ◽  
Author(s):  
T. Murata ◽  
K. Aritake ◽  
Y. Tsubosaka ◽  
T. Maruyama ◽  
T. Nakagawa ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Signal Enhancement ◽  
Acute Lung Inflammation ◽  
Therapeutic Application ◽  
Anti Inflammatory

Acute Lung Inflammation in Sickle Mice Is Mediated by Increase of CXC Chemokines and Matrix Metalloproteinases

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2483-2483
Author(s):  
Carla Fernanda Franco-Penteado ◽  
Carolina Lanaro ◽  
Dulcinéia M Albuquerque ◽  
Ana Paula Gimenes ◽  
Luiz Augusto C Passos ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Lung Inflammation ◽  
Intranasal Administration ◽  
Pcr Analysis ◽  
Acute Chest Syndrome ◽  
Control Group ◽  
Mrna Levels ◽  
Acute Lung Inflammation ◽  
Lps Challenge ◽  
Tnf Α

Abstract Studies in vitro, and in vivo using animal models show that leukocytes play a key role in vasoocclusion and clinical research suggests that high leukocyte counts correlate with mortality, stroke and acute chest syndrome in sickle cell disease (SCD). Lungs are particularly vulnerable to vaso-occlusive events because of their anatomic features in SCD. Transgenic mice expressing exclusively human sickle hemoglobin (SS) are well-established models for the study of vascular inflammation. Previous studies have shown that systemic LPS challenge causes exaggerated inflammation, including increased serum and broncoalveolar lavage (BAL) TNF-α and IL-1 cytokines and sVCAM-1 in sickle mice. The aim of this study was to examine the contribution of acute airway inflammation in SCD using SS mice and the role of chemokines and matrix metalloproteinases (MMPs) in this process. Acute lung inflammation and injury were induced by intranasal administration of lipopolysaccharide (LPS, 50 μl of 250 μg/ml) in control (C57BL/6) and SS mice. The vehicle mice group received a similar volume of sterile PBS. BAL was performed 4 h after LPS challenge. qRT-PCR analysis was used to examine gene expression and ELISA protein production. The intranasal administration of LPS to mice triggered a huge influx of leukocytes (neutrophils, NS) in BAL of control and SS mice compared with the respective vehicle groups, but this influx was greater in SS mice, when compared with control mice (1.4 ± 0.06 vs 0.66 ± 0.12 WBCx106/BAL); p=0.0006, 1.06 ± 0.1 vs 0.40 ±0.12 NSx106/BAL; p=0.004, respectively). At baseline levels, KC and MIP-2 chemokines (functional homologues of human IL-8 in mice) are higher in BAL fluid of SS mice compared to control mice (186.6 ± 14.1 pg/ml vs 14.1 ± 5.8 pg/ml; 41.2 ± 7.9 pg/ml vs 11.4 ± 7.3 pg/ml, p=, respectively). Corresponding with influx of NS, lung lavage levels of KC and MIP-2 were significantly higher in SS BALF compared to control mice (2491 ± 454 pg/ml vs 798.1 vs 98.2 pg/ml; 1726 ± 307 pg/ml vs 887.3 ± 149.5 pg/ml, respectively). Enhanced levels of TNF-α were also observed at baseline and after LPS instillation compared to those of the control mice (20.8 ± 8.8 pg/ml vs 2.5 ± 1.6 pg/ml; 4250 ± 636 pg/ml vs 1585 ± 263 pg/ml, respectively). Instillation of LPS markedly increased KC, TNF-α, MMP-8, MMP-9 and TIMP-1 mRNA levels in the lungs of control and SS mice compared to animals that received PBS instead of LPS (Control, KC: 0.19 ± 0.047 vs 0.01 ± 0.005; TNF-α: 0.30 ± 0.07 vs 0.01 ± 0.002; MMP-8: 0.2 ± 0.06 vs 0.016 ± 0.004; MMP-9: 0.22 ± 0.03 vs 0.08 ± 0.01; TIMP-1: 0.32 ± 0.06 vs 0.09 ± 0.03); (SS, KC: 0.42 ± 0.1 vs 0.039 ± 0.02; TNF-α: 0.23 ± 0.025 vs 0.02 ± 0.007; MMP-8: 0.42 ± 0.06 vs 0.06 ± 0.03; MMP-9: 0.49 ± 0.11 vs 0.11 ± 0.05; TIMP-1: 0.49 ± 0.11 vs 0.09 ± 0.03). However, the LPS-induced KC, MMP-8 and MMP-9 expression was significantly higher in SS mice lung compared than that of the control group (p<0.05). Lung MMP-2, MMP-12 and TIMP-2 gene expressions were similar in the PBS and LPS groups and were not significantly different between SS and control mice. Our results indicate that chemokines and MMPs are critically involved in the recruitment of neutrophils to the lung following LPS challenge, and suggest that these inflammatory mediators may play a role in the development of pulmonary diseases in SCD. The findings from this study provide further support to the claim that a proinflammatory state is present in SCD and have important implications for the pathophysiology of lung injury in SCD.

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