scholarly journals CD116+ fetal precursors migrate to the perinatal lung and give rise to human alveolar macrophages

2022 ◽  
Vol 219 (2) ◽  
Author(s):  
Elza Evren ◽  
Emma Ringqvist ◽  
Jean-Marc Doisne ◽  
Anna Thaller ◽  
Natalie Sleiers ◽  
...  
Keyword(s):  
Alveolar Macrophage ◽  
Alveolar Macrophages ◽  
Fetal Liver ◽  
Fetal Lung ◽  
Gene Signature ◽  
Human Macrophage ◽  
Humanized Mouse Model ◽  
Human Alveolar Macrophages ◽  
Macrophage Precursors

Despite their importance in lung health and disease, it remains unknown how human alveolar macrophages develop early in life. Here we define the ontogeny of human alveolar macrophages from embryonic progenitors in vivo, using a humanized mouse model expressing human cytokines (MISTRG mice). We identified alveolar macrophage progenitors in human fetal liver that expressed the GM-CSF receptor CD116 and the transcription factor MYB. Transplantation experiments in MISTRG mice established a precursor–product relationship between CD34−CD116+ fetal liver cells and human alveolar macrophages in vivo. Moreover, we discovered circulating CD116+CD64−CD115+ macrophage precursors that migrated from the liver to the lung. Similar precursors were present in human fetal lung and expressed the chemokine receptor CX3CR1. Fetal CD116+CD64− macrophage precursors had a proliferative gene signature, outcompeted adult precursors in occupying the perinatal alveolar niche, and developed into functional alveolar macrophages. The discovery of the fetal alveolar macrophage progenitor advances our understanding of human macrophage origin and ontogeny.

scholarly journals Tissue factor and factor VII messenger RNAs in human alveolar macrophages: effects of breathing ozone

Blood ◽  
1990 ◽  
Vol 75 (1) ◽  
pp. 122-127 ◽  
Author(s):  
MP McGee ◽  
R Devlin ◽  
G Saluta ◽  
H Koren
Keyword(s):  
Alveolar Macrophage ◽  
Tissue Factor ◽  
Alveolar Macrophages ◽  
Factor Vii ◽  
Fibrinopeptide A ◽  
Factor Activity ◽  
Tissue Factor Activity ◽  
Mrna Concentration ◽  
Human Alveolar Macrophages

Abstract This study was performed to determine if genes for tissue factor and factor VII proteins are expressed and regulated in vivo in lung macrophages during inflammation. Human alveolar macrophages and alveolar fluids were obtained 18 hours after healthy male adults were exposed, for 2 hours during intermittent exercise, to either air or air with 0.4 ppm ozone, added as a model toxic respiratory agent. Messenger RNA (mRNA) for both tissue factor and factor VII were demonstrated in macrophages isolated after subjects were exposed to unpolluted control air. With the same subjects examined after breathing ozone, the following changes were observed: tissue factor mRNA concentration in macrophages increased 2.6 +/- 0.47-fold. Factor VII mRNA concentration was reduced 0.64 +/- 0.24-fold. Total numbers of macrophages recovered did not change significantly. Ratios of nuclear:cytoplasmic areas of cytocentrifuged macrophages were augmented by 24.8% +/- 3%, giving morphometric evidence that immature cell forms increased in the population. In the lavage, tissue factor activity was increased 2.1 +/- 0.3-fold, while amounts of lipid phosphorous, which estimate total membrane lipids, and estimated volumes of alveolar fluid were not significantly changed. Factor VII activity and fibrinopeptide A levels in lavage were increased approximately twofold. These results using rapidly isolated, noncultured cells indicate that tissue factor and factor VII mRNA are synthesized in the alveolar macrophage population in vivo. In addition, evidence was found that as a result of breathing ozone, a shift in alveolar macrophage maturity occurred in association with tissue factor mRNA, tissue factor activity, and factor VII activity increases, and with formation of fibrinopeptide A in alveolar fluids.

scholarly journals Tissue factor and factor VII messenger RNAs in human alveolar macrophages: effects of breathing ozone

Blood ◽  
1990 ◽  
Vol 75 (1) ◽  
pp. 122-127
Author(s):  
MP McGee ◽  
R Devlin ◽  
G Saluta ◽  
H Koren
Keyword(s):  
Alveolar Macrophage ◽  
Tissue Factor ◽  
Alveolar Macrophages ◽  
Factor Vii ◽  
Fibrinopeptide A ◽  
Factor Activity ◽  
Tissue Factor Activity ◽  
Mrna Concentration ◽  
Human Alveolar Macrophages

This study was performed to determine if genes for tissue factor and factor VII proteins are expressed and regulated in vivo in lung macrophages during inflammation. Human alveolar macrophages and alveolar fluids were obtained 18 hours after healthy male adults were exposed, for 2 hours during intermittent exercise, to either air or air with 0.4 ppm ozone, added as a model toxic respiratory agent. Messenger RNA (mRNA) for both tissue factor and factor VII were demonstrated in macrophages isolated after subjects were exposed to unpolluted control air. With the same subjects examined after breathing ozone, the following changes were observed: tissue factor mRNA concentration in macrophages increased 2.6 +/- 0.47-fold. Factor VII mRNA concentration was reduced 0.64 +/- 0.24-fold. Total numbers of macrophages recovered did not change significantly. Ratios of nuclear:cytoplasmic areas of cytocentrifuged macrophages were augmented by 24.8% +/- 3%, giving morphometric evidence that immature cell forms increased in the population. In the lavage, tissue factor activity was increased 2.1 +/- 0.3-fold, while amounts of lipid phosphorous, which estimate total membrane lipids, and estimated volumes of alveolar fluid were not significantly changed. Factor VII activity and fibrinopeptide A levels in lavage were increased approximately twofold. These results using rapidly isolated, noncultured cells indicate that tissue factor and factor VII mRNA are synthesized in the alveolar macrophage population in vivo. In addition, evidence was found that as a result of breathing ozone, a shift in alveolar macrophage maturity occurred in association with tissue factor mRNA, tissue factor activity, and factor VII activity increases, and with formation of fibrinopeptide A in alveolar fluids.

Exogenous surfactant changes the phenotype of alveolar macrophages in mice

2001 ◽  
Vol 280 (4) ◽  
pp. L689-L694 ◽  
Author(s):  
Boris W. Kramer ◽  
Alan H. Jobe ◽  
Machiko Ikegami
Keyword(s):  
Alveolar Macrophage ◽  
Alveolar Macrophages ◽  
Scavenger Receptor ◽  
Exogenous Surfactant ◽  
Surface Markers ◽  
Macrophage Phenotype ◽  
Surfactant Treatment ◽  
Class A ◽  
Scavenger Receptor Class

Alveolar macrophages are essential for the maintenance of surfactant homeostasis. We asked whether surfactant treatment would change alveolar macrophage number and whether the alveolar macrophage phenotype would become activated or apoptotic when challenged in vivo with exogenous surfactant. Surfactant pool size in mice was increased by repetitive surfactant treatments containing 120 mg/kg (110 μmol/kg) saturated phosphatidylcholine. The number of alveolar macrophages recovered by alveolar lavage decreased after the first dose by 49% and slightly increased after the second and third doses. Up to 28.5% of the macrophages became large and foamy, and their appearance normalized within 12 h. Surfactant treatment did not increase the percent of apoptotic or necrotic cells. The alveolar macrophages were not activated as indicated by no change in expression of CD14, CD16, CD54, CD95, and scavenger receptor class A types I and II after surfactant treatment. Surfactant treatment in healthy mice transiently changed the phenotype of alveolar macrophages to large and foamy without indications of changes in the surface markers characteristic of activation.

scholarly journals Constitutive nitric oxide production by rat alveolar macrophages

1998 ◽  
Vol 274 (3) ◽  
pp. L360-L368 ◽  
Author(s):  
P. R. Miles ◽  
L. Bowman ◽  
A. Rengasamy ◽  
L. Huffman
Keyword(s):  
Nitric Oxide ◽  
Alveolar Macrophage ◽  
Alveolar Macrophages ◽  
Lung Surfactant ◽  
Calcium Ionophore ◽  
Cell Types ◽  
Alveolar Type ◽  
No Production ◽  
No Formation

Results from previous studies suggest that alveolar macrophages must be exposed to inflammatory stimuli to produce nitric oxide (⋅ NO). In this study, we report that naive unstimulated rat alveolar macrophages do produce ⋅ NO and attempt to characterize this process. Western blot analysis demonstrates that the enzyme responsible is an endothelial nitric oxide synthase (eNOS). No brain or inducible NOS can be detected. The rate of ⋅ NO production is ∼0.07 nmol ⋅ 106cells−1 ⋅ h−1, an amount that is less than that produced by the eNOS found in alveolar type II or endothelial cells. Alveolar macrophage ⋅ NO formation is increased in the presence of extracellularl-arginine, incubation medium containing magnesium and no calcium, a calcium ionophore (A-23187), or methacholine. ⋅ NO production is inhibited by N G-nitro-l-arginine methyl ester (l-NAME) but not by N G-nitro-l-arginine,l- N 5-(1-iminomethyl)ornithine hydrochloride, or aminoguanidine. Incubation with ATP, ADP, or histamine also inhibits ⋅ NO formation. Some of these properties are similar to and some are different from properties of eNOS in other cell types. Cellular ⋅ NO levels do not appear to be related to ATP or lactate content. Alveolar macrophage production of ⋅ NO can be increased approximately threefold in the presence of lung surfactant or its major component, dipalmitoyl phosphatidylcholine (DPPC). The DPPC-induced increase in ⋅ NO formation is time and concentration dependent, can be completely inhibited by l-NAME, and does not appear to be related to the degradation of DPPC by alveolar macrophages. These results demonstrate that unstimulated alveolar macrophages produce ⋅ NO via an eNOS and that lung surfactant increases ⋅ NO formation. This latter effect may be important in maintaining an anti-inflammatory state in vivo.

Production of Chemotactic Factor(s) by in vivo Cultured Human Alveolar Macrophages

CHEST Journal ◽  
1979 ◽  
Vol 75 (2) ◽  
pp. 224
Author(s):  
William W. Merrill ◽  
Gary P. Naegel ◽  
Richard A. Matthay ◽  
Herbert Y. Reynolds
Keyword(s):  
Alveolar Macrophages ◽  
Chemotactic Factor ◽  
Human Alveolar Macrophages

Metabolic adaptations of human alveolar macrophages upon activation by lipopolysaccharide in vivo

2021 ◽  
Author(s):  
Natasja A. Otto ◽  
Joe M. Butler ◽  
Ivan Ramirez‐Moral ◽  
Jacobien J. Hoogerwerf ◽  
Riekelt H. Houtkooper ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Metabolic Adaptations ◽  
Human Alveolar Macrophages

scholarly journals Exogenous Heat-Killed Escherichia coli Improves Alveolar Macrophage Activity and Reduces Pneumocystis carinii Lung Burden in Infant Mice

2007 ◽  
Vol 75 (7) ◽  
pp. 3382-3393 ◽  
Author(s):  
Kerry M. Empey ◽  
Melissa Hollifield ◽  
Beth A. Garvy
Keyword(s):  
Escherichia Coli ◽  
Alveolar Macrophage ◽  
Alveolar Macrophages ◽  
Cytokine Production ◽  
Pneumocystis Carinii ◽  
Effector Cells ◽  
Macrophage Activity ◽  
Adult Mice

ABSTRACT Pneumocystis carinii is an opportunistic fungal pathogen that causes life-threatening pneumonia in immunocompromised individuals. Infants appear to be particularly susceptible to Pneumocystis pulmonary infections. We have previously demonstrated that there is approximately a 3-week delay in the clearance of Pneumocystis organisms from pup mouse lungs compared to that in adults. We have further shown that there is approximately a 1-week delay in alveolar macrophage activation in pups versus adult mice. Alveolar macrophages are the primary effector cells responsible for the killing and clearance of Pneumocystis, suggesting that pup alveolar macrophages may be involved in the delayed clearance of this organism. Alveolar macrophages cultured in vitro with Pneumocystis alone demonstrate little to no activation, as indicated by a lack of cytokine production. However, when cultured with lipopolysaccharide (LPS) or zymosan, cytokine production was markedly increased, suggesting that pup alveolar macrophages are specifically unresponsive to Pneumocystis organisms rather than being intrinsically unable to become activated. Furthermore, pup mice treated with aerosolized, heat-killed Escherichia coli in vivo were able to clear Pneumocystis more efficiently than were control mice. Together, these data suggest that while pup alveolar macrophages are unresponsive to P. carinii f. sp. muris organisms, they are capable of activation by heat-killed E. coli in vivo, as well as LPS and zymosan in vitro. The lack of response of pup mice to P. carinii f. sp. muris may reflect protective mechanisms specific to the developing pup lung, but ultimately it results in insufficient clearance of Pneumocystis organisms.

scholarly journals Initiation of the extrinsic pathway of coagulation by human and rabbit alveolar macrophages: a kinetic study

Blood ◽  
1989 ◽  
Vol 74 (5) ◽  
pp. 1583-1590 ◽  
Author(s):  
MP McGee ◽  
R Wallin ◽  
FB Wheeler ◽  
H Rothberger
Keyword(s):  
Alveolar Macrophage ◽  
Alveolar Macrophages ◽  
Plasma Concentrations ◽  
Factor Xa ◽  
Factor Vii ◽  
Factor X ◽  
Extrinsic Pathway ◽  
Activation Rate ◽  
Factor X Activation

We examined assembly and expression of the factor X activating complex on human and rabbit alveolar macrophages. Kinetic parameters of the factor X activating reaction were determined by functional titrations of factors VII and X with macrophage tissue factor (TF) added. We found rapid activation of factor X to Xa on alveolar macrophage surfaces. Detection of rapid factor Xa formation on macrophages required addition of exogenous factors VII and X. At plasma concentrations of the purified factors, factor Xa was formed on freshly isolated macrophages at approximately 5.4 pmol/min/10(6) cells. After macrophage maturation in culture for 20 hours with LPS (endotoxin) added, the factor X activation rate was increased two- to sixfold. The km' (apparent km) of TF-factor VII enzymatic complexes assembled on alveolar macrophages for factor X were (258 +/- 55 and 475 +/- 264 nmol/L for human and rabbit cells, respectively). The km' did not change during macrophage maturation in culture, but V'max (apparent Vmax) was consistently increased. The K1/2 of human factor VII (concentrations giving half maximal rates of factor X activation) for the interaction with human and rabbit alveolar macrophage TF were 0.191 +/- 0.096 and 1.7 +/- 0.7 etamol/L, respectively. The K1/2 were not significantly changed after maturation, whereas rates of Xa formation at saturation with factor VII were increased. The fast rates of factor X activation observed at physiologic concentrations of plasma-derived factors VII and X indicate that TF on alveolar macrophages is likely to provide sites for binding of factor VII and activation of factor X in vivo during clotting reactions associated with alveolar edema and inflammation.

scholarly journals Wnt/β-catenin signaling regulates lipopolysaccharide-altered polarizations of RAW264.7 cells and alveolar macrophages in mouse lungs

2021 ◽  
Vol 19 ◽  
pp. 205873922110593
Author(s):  
Jiali Yang ◽  
Ying Wang ◽  
Dandan Yang ◽  
Jia Ma ◽  
Shuang Wu ◽  
...  
Keyword(s):  
Alveolar Macrophage ◽  
Alveolar Macrophages ◽  
Macrophage Polarization ◽  
Raw264.7 Cells ◽  
M1 Polarization ◽  
Inflammatory Phenotype ◽  
Inflammatory State ◽  
Anti Inflammatory

Introduction Macrophages are capable of exerting both proinflammatory and anti-inflammatory functions in response to distinct environmental stimuli, by polarizing into classically inflammatory state (M1) and anti-inflammatory phenotype (M2), respectively. The Wnt/β-catenin signaling plays an important role in the tissue homeostasis and immune regulations, including the macrophage polarizations. However, the molecular mechanism of Wnt/β-catenin signaling in regulating alveolar macrophage polarization in an inflammatory state remains unclear. Methods The Wnt/β-catenin signaling-altered phenotypes of murine macrophage-like RAW264.7 cells in vitro and alveolar macrophage in vivo in both of naïve and lipopolysaccharide-induced inflammation states were accessed by immunoblotting and immunostaining assays. Results The activation of Wnt/β-catenin signaling inhibited macrophage M1 polarization, but promoted alternative M2 polarization in murine RAW264.7 cells under a naïve state. Interestingly, in an LPS-induced inflammation condition, the enhanced Wnt/β-catenin activity suppressed both M1 and M2 polarizations in RAW264.7 cells in vitro, and primary alveolar macrophages of LPS-challenged mice in vivo. Molecular analysis further demonstrated an involvement of Stat signing in regulating Wnt/β-catenin signaling-altered polarizations in mouse alveolar macrophages. Conclusion These results suggest a mechanism by which Wnt/β-catenin signaling modulates macrophage polarization in an inflammation state by regulating the Stat signaling pathway.

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