Characterization and quantification of alveolar monocyte-like cells in human chronic inflammatory lung disease

Krombach, Fritz; Gerlach, J. Tilman; Padovan, Claudio S.; Burges, Alexander; Behr, Jürgen; Beinert, T.; Vogelmeier, Claus

doi:10.1183/09031936.96.09050984

Cited by 55 publications

(38 citation statements)

References 42 publications

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“…Although we did not examine alveolar macrophages in this study, the presence of SP-A responses in their precursor cells, peripheral blood monocytes, and the THP-1 cells (a commonly used surrogate), is relevant. Cells obtained from the alveolar spaces of individuals with diseased lungs often exhibit properties more similar to those of peripheral blood monocytes than alveolar macrophages from the lungs of normal subjects (26,39). We speculate that the alterations in the SP-A levels (8,11) found in many of these diseases may result in the observed changes in MMP-9 (1,40).…”

Section: Discussionmentioning

confidence: 93%

Surfactant protein A increases matrix metalloproteinase-9 production by THP-1 cells

Lara

Umstead

Davis

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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trix metalloproteinase (MMP)-9 from alveolar macrophages is a major source of elastolytic activity in the lung. It is increased in the bronchoalveolar lavage fluid of patients with emphysema. Although the importance of macrophage-derived elastolytic activity in the pathogenesis of emphysema is well established, questions remain about MMP-9 regulation and activity. Because surfactant protein A (SP-A) is capable of modulating other functions of human monocytic cells, we hypothesized that SP-A may regulate MMP-9 expression. Vitamin D 3-differentiated THP-1 cells and peripheral blood mononuclear cells were stimulated in vitro with several concentrations of SP-A for different incubation times. MMP-9 mRNA expression was measured by dot-blot analysis, gelatinolytic activity in the medium was determined by gel zymography, protein expression was determined by ELISA, and a specific MMP-9 activity assay was used to measure the state of activation of this enzyme in the cell supernatants. SP-A induced the expression of MMP-9 in both cell types, the effect was time and dose dependent, and MMP-9 was released in its zymogen form. On the basis of results of neutralizing antibody studies, we believe that SP-A action is mediated through Toll-like receptor-2. Even though the biological meaning of these findings remains to be elucidated, these observations suggest the presence of a novel, locally controlled mechanism by which MMP-9 levels may be regulated in alveolar macrophages. We speculate that SP-A may influence the protease/antiprotease balance in the lungs of patients with quantitative and/or qualitative changes in surfactant constituents favoring an abnormal breakdown of extracellular matrix components. gelatinase; macrophage; chronic obstructive pulmonary disease

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Section: Discussionmentioning

confidence: 93%

Surfactant protein A increases matrix metalloproteinase-9 production by THP-1 cells

Lara

Umstead

Davis

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Next we asked whether inhibition of FA synthesis influences macrophage ultrastructure. It is known that monocyte differentiation increases the volume of the cells and the number of intracellular organelles (15)(16)(17). Accordingly, electron microscopy showed monocytes as small round cells with short filapodia and a big nucleus (Fig.…”

Section: Phosphatidylcholine and Phosphatidylethanolamine Synthesis Amentioning

confidence: 92%

Induction of fatty acid synthesis is a key requirement for phagocytic differentiation of human monocytes

Ecker

Liebisch

Englmaier

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

205

175

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Monocytes are precursors of macrophages. Here we demonstrate that macrophage colony-stimulating factor (M-CSF)-dependent differentiation of primary human monocytes from healthy volunteers induces transcription of SREBP-1c target genes required for fatty acid (FA) biosynthesis and impairs transcription of SREBP-2 target genes required for cholesterol synthesis. Detailed lipid metabolic profiling showed that this transcriptional regulation leads to a dramatically increased fatty acid synthesis as driving force for enhanced phospholipid synthesis. During cell differentiation the major lipid class switches from cholesterol in monocytes to phosphatidylcholine in macrophages. Ultrastructural analysis revealed that this transcriptional and metabolic regulation is essential for development of macrophage filopodia and cellular organelles including primary lysosomes, endoplasmic reticulum, and Golgi network. Additional functional studies showed that suppression of fatty acid synthesis prevents phagocytosis representing a central macrophage function. Therefore induction of fatty acid synthesis is a key requirement for phagocyte development and function.

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“…Monocyte-like cells have been observed in various inflammatory lung conditions [7,10,26]. Similarly, a population of monocytes with reduced phagocytic capacity and increased expression of markers of dendritic cell maturation was described in sputum from healthy volunteers following LPS inhalation [27], and a ''small sputum macrophage'' was reported in patients with COPD [28].…”

Section: Discussionmentioning

confidence: 99%

A novel subpopulation of monocyte-like cells in the human lung after lipopolysaccharide inhalation

Brittan¹,

Barr²,

Morris³

et al. 2012

Eur Respir J

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The co-ordinated recruitment of monocyte subpopulations, neutrophils and regulatory T-cells (Tregs) during the early stages of human acute lung inflammation remains poorly understood. We therefore performed a detailed characterisation of these lineages in the blood and lungs in a model of human acute lung inflammation.Healthy volunteers inhaled lipopolysaccharide (LPS) or saline (n56 for each group). Blood was collected at 0, 2, 4, 6 and 8 h and bronchoscopy with bronchoalveolar lavage (BAL) performed at 8 h. Multiparameter flow cytometry was used to characterise monocyte subpopulations, neutrophils and Tregs in the blood and lung.Inhalation of LPS was associated with significant blood and BAL fluid neutrophilia. Blood populations of monocyte subpopulations and Tregs were unaltered by LPS. In contrast, LPS induced an accumulation of a pulmonary monocyte-like cell (PMLC) population, which was further subdivided into ''inducible'' CD14 ++ CD16 -and ''resident'' CD14 ++ CD16 + subsets. Inducible PMLCs were significantly increased following LPS inhalation (p50.0046), whereas resident PMLCs were unchanged. In addition, we noted a significant decrease in Tregs in BAL fluid with LPS inhalation (p50.027).The early stages of LPS-induced inflammation in humans is characterised by pulmonary accumulation of a novel inducible monocyte-like subpopulation, accompanied by significant changes in both neutrophil and Treg numbers.

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Characterization and quantification of alveolar monocyte-like cells in human chronic inflammatory lung disease

Abstract: In summary, our flow cytometric data strongly support the view that considerable numbers of blood monocytes are recruited to the bronchoalveolar space in patients with chronic inflammatory lung disease. Eur Respir J., 1996, 9, 984-991.

Cited by 55 publications

References 42 publications

Surfactant protein A increases matrix metalloproteinase-9 production by THP-1 cells

Surfactant protein A increases matrix metalloproteinase-9 production by THP-1 cells

Induction of fatty acid synthesis is a key requirement for phagocytic differentiation of human monocytes

A novel subpopulation of monocyte-like cells in the human lung after lipopolysaccharide inhalation

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