Role of lymphatics in removal of sheep lung surfactant lipid

1983 ◽  
Vol 54 (4) ◽  
pp. 984-988 ◽  
Author(s):  
M. M. Tarpey ◽  
H. M. O'Brodovich ◽  
S. L. Young
Keyword(s):  
Lung Tissue ◽  
Specific Activity ◽  
Mediastinal Lymph Node ◽  
Lung Surfactant ◽  
Lavage Fluid ◽  
Tissue Lipids ◽  
Surfactant Lipid ◽  
Lymph Lipid ◽  
Lung Lymph

To study the role of lung lymphatics in the removal of surfactant lipid from the sheep lung, we injected [1–14C]palmitate intravenously into six animals previously fitted with a cannula draining the caudal mediastinal lymph node. Lung lymph was collected for 100 h after injection of radiolabel. We obtained alveolar lavage material through a tracheostomy in four other animals after intravenous injection of [9,10–3H]palmitate. We measured radioactivity at several time points in lipid extracts from lymph, lavage fluid, and lung tissue. Alveolar lavage disaturated phosphatidylcholine (DSPC) specific activity peaked at about 40 h and was reduced to 30% of this value by 82 h. About 2% of the injected radiolabel was incorporated into lung tissue lipids. Only 4% of the level of labeling achieved in lung tissue lipids was found in lung lymph lipid during 100 h of lymph collection. Sixty-three percent of radiolabel in lymph lipid was recovered in phospholipids, and 29% of phospholipid radiolabel was found in DSPC. The distribution of phosphorus and palmitate radiolabel in lung lymph phospholipid did not closely resemble that of surfactant lipid. No rise in lung lymph DSPC specific activity was observed following the peak in lavage specific activity. If surfactant lipid is removed from the alveolar compartment without extensive recycling, then we conclude that the lung lymphatics do not play a major role in the clearance of surfactant lipid from the alveolar surface.

scholarly journals Effects of CX3CL1 inhibition on murine bleomycin-induced interstitial pneumonia

2020 ◽  
Vol 18 ◽  
pp. 205873922095990
Author(s):  
Soichi Yamada ◽  
Shion Miyoshi ◽  
Junko Nishio ◽  
Satoshi Mizutani ◽  
Zento Yamada ◽  
...  
Keyword(s):  
Interstitial Pneumonia ◽  
T Cell Activation ◽  
Lung Tissue ◽  
Cell Activation ◽  
Immunohistochemical Analysis ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Novel Therapy ◽  
Tissue Sections

Background: Treatment for interstitial pneumonia (IP) associated with collagen diseases has not been established. There is a need to elucidate the pathogenesis of IP and develop a novel therapy. We aimed to clarify the role of chemokine (C-X3-C motif) ligand 1 (CX3CL1, also known as fractalkine) in IP. Methods: Bleomycin (BLM) was intratracheally administered to C57BL/6 mice to induce IP. For treatment with control Ab or anti-CX3CL1 mAb, the mice were administered either Ab three times per week for 2 weeks from the day of BLM administration until euthanasia. Expressions of CX3CL1 and its unique receptor CX3CR1 in the lung tissue were examined by immunohistochemical analysis. Cellular infiltration and lung fibrosis were evaluated based on hematoxylin-eosin-staining and Sirius red staining of the lung tissue sections, respectively. Bronchoalveolar lavage fluid (BALF) cells were analyzed by flow cytometry. Results: CX3CL1 and CX3CR1 were strongly expressed in the lung tissue from mice with BLM-induced IP (BLM-IP). Treatment with anti-CX3CL1 mAb did not significantly alter inflammatory cell infiltration or fibrosis in the lung tissue. However, the number of M1-like macrophages in BALF was decreased and surface CD3 expression on T cells was increased by anti-CX3CL1 mAb treatment. Conclusions: Inhibition of CX3CL1 decreased inflammatory cells and may attenuate T cell activation in BALF. CX3CL1 inhibitor may have the potential to suppress the infiltration and activation of immune cells in IP.

scholarly journals Inhibition of Prostaglandin F2α Receptors Exaggerates HCl-Induced Lung Inflammation in Mice

2021 ◽  
Vol 22 (23) ◽  
pp. 12843
Author(s):  
Toko Maehara ◽  
Ko Fujimori
Keyword(s):  
Umbilical Vein ◽  
Lung Surfactant ◽  
Neutrophil Migration ◽  
Prostaglandin F2α ◽  
Lavage Fluid ◽  
Clinical Feature ◽  
Lung Edema ◽  
Induced Expression ◽  
Respiratory Dysfunction

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe respiratory disorders that are caused by aspiration, sepsis, trauma, and pneumonia. A clinical feature of ALI/ARDS is the acute onset of severe hypoxemia, and the mortality rate, which is estimated at 38–50%, remains high. Although prostaglandins (PGs) are detected in the bronchoalveolar lavage fluid of patients with ALI/ARDS, the role of PGF2α in ALI remains unclear. We aimed to clarify the role of PGF2α/PGF2α receptor (FP) signaling in acid-induced ALI using an FP receptor antagonist, AL8810. Intratracheal injection of hydrochloric acid (HCl) increased neutrophil migration into the lungs, leading to respiratory dysfunction. Pre-administration of AL8810 further increased these features. Moreover, pre-treatment with AL8810 enhanced the HCl-induced expression of pro-inflammatory cytokines and neutrophil migratory factors in the lungs. Administration of HCl decreased the gene expression of lung surfactant proteins, which was further reduced by co-administration of AL8810. Administration of AL8810 also increased lung edema and reduced mRNA expression of epithelial sodium channel in the lungs, indicating that AL8810 reduced fluid clearance. Furthermore, AL8810 also increased lipopolysaccharide-induced expression of adhesion molecules such as intracellular adhesion molecule-1 and E-selectin in human umbilical vein endothelial cells. These results indicate that inhibition of FP receptors by AL8810 exacerbated HCl-induced ALI.

scholarly journals Chronic pharmacological antagonism of murine GM-CSF-R-alpha does not replicate the Pulmonary Alveolar Proteinosis phenotype but does alter lung surfactant turnover

2021 ◽  
Author(s):  
Dominic J Corkill ◽  
Alan N Hunt ◽  
Mary Jane Hinrichs ◽  
Nicholas White ◽  
Marlon Rebelatto ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Pulmonary Alveolar Proteinosis ◽  
Inflammatory Diseases ◽  
Lung Surfactant ◽  
Lavage Fluid ◽  
Α Subunit ◽  
Knock Out ◽  
Gm Csf ◽  
Significant Impairment ◽  
Alveolar Proteinosis

Granulocyte macrophage colony stimulating factor (GM-CSF) is a key participant in, and a clinical target for, the treatment of inflammatory diseases including rheumatoid arthritis (RA).  Therapeutic inhibition of GM-CSF signalling using monoclonal antibodies to the α-subunit of the GM-CSF receptor (GMCSFRα) has shown clear benefit in patients with RA, giant cell arteritis (GCA)  and some efficacy in severe SARS-CoV-2 infection.  However, GM-CSF autoantibodies are associated with the development of pulmonary alveolar proteinosis (PAP), a rare lung disease characterised by alveolar macrophage (AM) dysfunction and the accumulation of surfactant lipids.  We assessed how the anti-GMCSFRα approach might impact surfactant turnover in the airway.  Female C57Bl/6J mice received a mouse-GMCSFRα blocking antibody (CAM-3003) twice per week for up to 24 weeks. A parallel, comparator cohort of the mouse PAP model, GMCSFRβ knock-out (KO), was maintained up to 16 weeks.  We assessed lung tissue histopathology alongside lung phosphatidylcholine (PC) metabolism using stable isotope lipidomics.  GMCSFRβ KO mice reproduced the histopathological and biochemical features of PAP, accumulating surfactant PC in both broncho-alveolar lavage fluid (BALF) and lavaged lung tissue.  The incorporation pattern of methyl-D9-choline showed impaired catabolism and not enhanced synthesis.  In contrast, chronic supra-pharmacological CAM-3003 exposure (100mg/kg) over 24 weeks did not elicit a histopathological PAP phenotype despite some changes in lung PC catabolism.  Lack of significant impairment of AM catabolic function supports clinical observations that therapeutic antibodies to this pathway have not been associated with PAP in clinical trials.

Role of peptidoleukotrienes in hypoxic pulmonary vasoconstriction in rats

1990 ◽  
Vol 259 (3) ◽  
pp. H751-H758 ◽  
Author(s):  
T. J. McDonnell ◽  
J. Y. Westcott ◽  
J. Czartolomna ◽  
N. F. Voelkel
Keyword(s):  
Lung Tissue ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Physiological Salt Solution ◽  
Slight Reduction ◽  
Lipoxygenase Inhibitor ◽  
Pulmonary Vasoconstriction ◽  
Eicosanoid Production

The role of leukotrienes in the mechanism of hypoxic pulmonary vasoconstriction (HPV) is controversial. To determine whether leukotriene C4 (LTC4) was produced during HPV, LTC4 levels were measured in individual samples of lung tissue, lung bronchoalveolar lavage fluid (BALF), and blood perfusate in isolated perfused lungs ventilated with normoxic or hypoxic gas mixtures. HPV was not associated with increased LTC4 in lung tissue or increased LTE4 in blood perfusate. Consistent with previous studies demonstrating elevated levels of LTC4 in pooled BALF fluid from hypoxic lungs, individual lung BALF samples demonstrated an elevation of LTC4 during hypoxia. However, the process of lung lavage alone stimulated eicosanoid production, with LTC4, 6-ketoprostaglandin F1 alpha, and thromboxane B2 levels being higher in lavaged compared to non-lavaged lungs. In lungs to which the lipoxygenase inhibitor AA 861 was added to the perfusate, a reduction in the lung tissue LTC4 levels was observed without any or only a slight reduction in HPV. To evaluate the physiological effects of LTC4 in the airways, exogenous LTC4 (1-1,000 ng) was added to the airways of both blood- and physiological salt solution-perfused lungs without any effect on the pulmonary artery pressure or a response to hypoxia. These results do not support the hypothesis that leukotrienes mediate HPV in the rat.

Differential permeability of endothelial and epithelial barriers to albumin flux

1979 ◽  
Vol 47 (6) ◽  
pp. 1315-1324 ◽  
Author(s):  
A. B. Gorin ◽  
P. A. Stewart
Keyword(s):  
Specific Activity ◽  
Membrane Damage ◽  
Endothelial Permeability ◽  
Lavage Fluid ◽  
Edema Formation ◽  
Lung Epithelial ◽  
Albumin Content ◽  
Epithelial Barriers ◽  
Lung Epithelial Permeability ◽  
Lung Lymph

We measured the flux of albumin between the vascular space and the pulmonary interstitial and luminal lining fluids in 20 adult sheep with chronic lung lymph fistulas. We sampled the bronchoalveolar lining layer by episodic fiberbronchoscopic lavage. A total of 62 alveolar lavages were performed at times ranging between 30 min and 60 h after intra-arterial injection of 100 microCi of 125I-labeled albumin. Samples of lymph and plasma were obtained simultaneously with lavage fluid, and the radioactivity and albumin content of all samples were measured and expressed as specific activity (counts/min . g albumin). We found that alveolar lavage fluid collected by our technique is not significantly contaminated by plasma or interstitial fluid proteins. Proteins present in alveolar lavage fluid and also present in plasma reach the alveolar space by a normal diffusive process, and not as a result of epithelial membrane damage occurring at the time of lavage. Lung epithelial permeability to albumin in small, but finite (4.3--5.8 x 10(-10) cm/s). Virtually all (greater than 92%) of resistance to albumin flux across the alveolocapillary membrane lies in the epithelial barrier. Increases in permeability of the respiratory epithelium, even minor, would have a marked effect on water and solute balance in the lung. Epithelial injury will potentiate pulmonary edema formation even in the presence of normal pulmonary microvascular pressure, plasma oncotic pressure, and endothelial permeability.

Role of vagal innervation on pulmonary surfactant system during fetal development

2009 ◽  
Vol 106 (5) ◽  
pp. 1641-1649 ◽  
Author(s):  
Luxmi Gahlot ◽  
Francis H. Y. Green ◽  
Anita Rigaux ◽  
Jennifer M. Schneider ◽  
Shabih U. Hasan
Keyword(s):  
Bronchoalveolar Lavage ◽  
Lung Tissue ◽  
Fetal Development ◽  
Pulmonary Surfactant ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Surfactant Proteins ◽  
Surfactant System ◽  
Vagal Innervation

Vagally mediated afferent feedback and compliant lungs (surfactant system) play vital roles in the establishment of adequate alveolar ventilation and pulmonary gas exchange at birth. Although the significance of vagal innervation in the establishment of normal breathing patterns is well recognized, the precise role of lung innervation in the maturation of the surfactant system remains unclear. The specific aim of the present study was to investigate whether vagal denervation compromises the surfactant system during fetal development. Experiments were performed on 12 time-dated fetal sheep: 8 underwent cervical vagal denervation, and 4 were sham operated. Vagal denervation was performed at 110–113 days gestation. Fetal lambs were instrumented in utero to record arterial pH and blood-gas tensions. The animals were delivered by cesarean section under general anesthesia between 130 and 133 days gestation (term ∼147 days). Lung samples were collected for wet-to-dry ratios, light and electron microscopy, and overall lung morphology. In addition, total proteins, total phospholipids, and surfactant proteins A and B were analyzed in both lung tissue and bronchoalveolar lavage fluid. Vagal denervation had no effect on alveolar architecture, including type II cells or the morphology of lamellar bodies within them. Furthermore, surfactant proteins A and B and total phospholipids were similar in lung tissue and bronchoalveolar lavage fluid between the two groups. A significant correlation was observed between circulating cortisol concentrations and surfactant proteins in the bronchoalveolar lavage fluid and lung tissue. We provide definitive evidence that vagal innervation at midgestation is not required for maturation of the pulmonary surfactant system during fetal development.

E. colipneumonia induces CD18-independent airway neutrophil migration in the absence of increased lung vascular permeability

2003 ◽  
Vol 285 (4) ◽  
pp. L879-L888 ◽  
Author(s):  
Evan S. Ong ◽  
Xiao-Pei Gao ◽  
Ning Xu ◽  
Dan Predescu ◽  
Arshad Rahman ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Vascular Injury ◽  
Lung Tissue ◽  
Neutrophil Migration ◽  
Fold Increase ◽  
Lavage Fluid ◽  
E Coli ◽  
Host Defense Response ◽  
The Relationship

We examined the relationship between neutrophil [polymorphonuclear leukocyte (PMN)] influx and lung vascular injury in response to Escherichia coli pneumonia. We assessed lung tissue PMN uptake by measuring myeloperoxidase and transvascular PMN migration by determining PMN counts in lung interstitium and bronchoalveolar lavage fluid (BALF) in mice challenged intratracheally with E. coli. Lung vascular injury was quantified by determining microvessel filtration coefficient ( Kf,c), a measure of vascular permeability. We addressed the role of CD18 integrin in the mechanism of PMN migration and lung vascular injury by inducing the expression of neutrophil inhibitory factor, a CD11/CD18 antagonist. In control animals, we observed a time-dependent sixfold increase in PMN uptake, a fivefold increase in airway PMN migration, and a 20-fold increase in interstitial PMN uptake at 6 h after challenge. Interestingly, Kf,cincreased minimally during this period of PMN extravasation. CD11/CD18 blockade reduced lung tissue PMN uptake consistent with the role of CD18 in mediating PMN adhesion to the endothelium but failed to alter PMN migration in the tissue. Moreover, CD11/CD18 blockade did not affect Kf,c. Analysis of BALF leukocytes demonstrated diminished oxidative burst compared with leukocytes from bacteremic mice, suggesting a basis for lack of vascular injury. The massive CD11/CD18-independent airway PMN influx occurring in the absence of lung vascular injury is indicative of an efficient host-defense response elicited by E. coli pneumonia.

Role of alveolar macrophage and migrating neutrophils in hemorrhage-induced priming for ALI subsequent to septic challenge

2006 ◽  
Vol 290 (1) ◽  
pp. L51-L58 ◽  
Author(s):  
Joanne Lomas-Neira ◽  
Chun-Shiang Chung ◽  
Mario Perl ◽  
Stephen Gregory ◽  
Walter Biffl ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lung Tissue ◽  
Peripheral Blood ◽  
Lavage Fluid ◽  
Tissue Samples ◽  
Relative Contribution ◽  
Inflammatory Protein ◽  
Tnf Α ◽  
Pulmonary Macrophages

Acute lung injury (ALI) is identified with the targeting/sequestration of polymorphonuclear leukocytes (PMN) to the lung. Instrumental to PMN targeting are chemokines [e.g., macrophage inflammatory protein-2 (MIP-2), keratinocyte-derived chemokine (KC), etc.] produced by macrophage, PMN, and other resident pulmonary cells. However, the relative contribution of resident pulmonary macrophages as opposed to PMN in inducing ALI is poorly understood. We therefore hypothesize that depletion of peripheral blood PMN and/or the oblation of a macrophage-mediated PMN chemokine signal (via macrophage deficiency) will reduce the inflammation and ALI observed in mice following hemorrhage (Hem) and subsequent sepsis (CLP) in our murine model of ALI. To examine this we pretreated mice with either 500 μg anti-mouse Gr1 antibody/animal (to deplete PMN) or subjected mice deficient in mature macrophage (B6C3Fe-a/a-CsF1op) to Hem (90 min at 35 ± 5 mmHg) followed by resuscitation. Twenty-four hours post-Hem, mice were subjected to CLP and killed 24 h later, and lung tissue samples were collected. Our data showed that in the absence of either peripheral blood PMN or mature tissue macrophages there was a suppression of IL-6, KC, and MIP-2 levels in lung tissue from Hem/CLP mice as well as a reduction in PMN influx to the lung and lung injury (bronchoalveolar lavage fluid protein). In contrast, lung tissue IL-10 and TNF-α levels were suppressed in the macrophage-deficient Hem/CLP mice compared with PMN-depleted Hem/CLP mice. Together, these data suggest that both the PMN and the macrophage are required to induce inflammation seen here, however, macrophage not PMN regulate the release of IL-10, independent of local changes in TNF.

scholarly journals Role and Regulation of Adipokines during Zymosan-Induced Peritoneal Inflammation in Mice

Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 4080-4085 ◽  
Author(s):  
Maria Pini ◽  
Melissa E. Gove ◽  
Joseph A. Sennello ◽  
Jantine W. P. M. van Baal ◽  
Lawrence Chan ◽  
...  
Keyword(s):  
Inflammatory Infiltrate ◽  
Peritoneal Lavage ◽  
Lavage Fluid ◽  
Wild Type ◽  
Cellular Infiltrate ◽  
Peritoneal Lavage Fluid ◽  
Peritoneal Inflammation ◽  
Leptin Deficiency ◽  
Cytokine Levels

Adipokines, cytokines mainly produced by adipocytes, are active participants in the regulation of inflammation. Administration of zymosan (ZY) was used to investigate the regulation and role of adipokines during peritonitis in mice. Injection of ZY led to a significant increase in leptin levels in both serum and peritoneal lavage fluid, whereas a differential trend in local vs. systemic levels was observed for both resistin and adiponectin. The role of leptin in ZY-induced peritonitis was investigated using leptin-deficient ob/ob mice, with and without reconstitution with exogenous leptin. Leptin deficiency was associated with delayed resolution of peritoneal inflammation induced by ZY, because ob/ob mice had a more pronounced cellular infiltrate in the peritoneum as well as higher and prolonged local and systemic levels of IL-6, TNFα, IL-10, and chemokine (C-X-C motif) ligand 2 compared with wild-type mice. Reconstitution with exogenous leptin exacerbated the inflammatory infiltrate and systemic IL-6 levels in ob/ob mice while inhibiting production of TNFα, IL-10, and chemokine (C-X-C motif) ligand 2. In contrast with the important role of leptin in regulating each aspect of ZY-induced peritonitis, adiponectin deficiency was associated only with a decreased inflammatory infiltrate, without affecting cytokine levels. These findings point to a complex role for adipokines in ZY-induced peritonitis and further emphasize the interplay between obesity and inflammation.

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