Characterization of a rat alveolar macrophage cell line that expresses a functional mannose receptor

Lane, Kirk B.; Egan, Brian; Vick, Sherell; Abdolrasulnia, Rasul; Shepherd, Virginia L.

doi:10.1002/jlb.64.3.345

Cited by 41 publications

(37 citation statements)

References 34 publications

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“…Man/Fucbinding lectins, such as the MFR have been well documented on mature macrophages (32,33); however, the MFR does not appear to play a role in PSG phagocytosis since phagocytosis was not inhibited by mannan, a known inhibitor of MFR. Furthermore, neither IFN-␥ nor dexamethasone altered the level of phagocytosis despite the fact that such mediators are known to regulate MFR mRNA and protein expression (33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

Alveolar Macrophages Bind and Phagocytose Allergen- Containing Pollen Starch Granules Via C-Type Lectin and Integrin Receptors: Implications for Airway Inflammatory Disease

Currie

Stewart

McWilliam

2000

The Journal of Immunology

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Recent studies suggest that IgE-independent mechanisms of airway inflammation contribute significantly to the pathophysiology of allergic airway inflammatory diseases such as asthma. Such mechanisms may involve direct interactions between inhaled allergens and cells of the respiratory tract such as macrophages, dendritic cells, and epithelial cells. In this study, we investigated receptor-mediated interactions occurring between alveolar macrophages and allergen-containing pollen starch granules (PSG). We report here that PSG are released from a range of grass species and are rapidly bound and phagocytosed by alveolar macrophages. Human monocyte-derived dendritic cells also bound PSG but no internalization was observed. Phagocytosis of PSG was dependent on Mg2+ and Ca2+ and was inhibited by neo-glycoproteins such as galactose-BSA and N-acetylgalactose-BSA. Partial inhibition of phagocytosis was also seen with the Arg-Gly-Asp-Ser (RGDS) motif and with an anti-CD18 mAb (OX42). The combination of both neo-glycoprotein and anti-CD18 achieved the greatest degree of inhibition (>90%). Together, these data suggest a role for both C-type lectins and β2-integrins in the binding and internalization of PSG. The consequences of this interaction included a rapid up-regulation of inducible NO synthase mRNA and subsequent release of NO by alveolar macrophages. Thus, receptor-mediated recognition of inhaled allergenic particles by alveolar macrophages may represent a potential mechanism for modulating the inflammatory response associated with allergic airway diseases such as asthma.

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Section: Discussionmentioning

confidence: 99%

Alveolar Macrophages Bind and Phagocytose Allergen- Containing Pollen Starch Granules Via C-Type Lectin and Integrin Receptors: Implications for Airway Inflammatory Disease

Currie

Stewart

McWilliam

2000

The Journal of Immunology

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“…RNA was transferred to a nylon membrane (Bio-Rad Zeta-Probe blotting membrane) using the standard capillary transfer method, prehybridized for 1 h with Quikhyb solution (Stratagene, Cedar Creek, TX), and hybridized overnight at 68°C. The ϳ5-kb MR transcript was identified by hybridization to a 32 P-labeled, 650-bp probe amplified from murine cDNA using primers described in Lane et al (30). The ϳ9-kb M6PR transcript was identified using a 686-bp probe amplified from the murine cDNA using primers derived from the murine CI-M6PR/IGFII receptor mRNA sequence as follows: sense, 5Ј-CATTTACACATGGGAAGCTG-3Ј, and antisense, 5Ј-GACCA-TTACAGAAGTCTGG-3Ј.…”

Section: Methodsmentioning

confidence: 99%

Mannose 6-Phosphate Receptor-mediated Uptake Is Defective in Acid Sphingomyelinase-deficient Macrophages

Dhami

Schuchman

2004

Journal of Biological Chemistry

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Progressive accumulation of lipid-laden macrophages is a hallmark of the acid sphingomyelinase (ASM)-deficient forms of Niemann-Pick disease (i.e. Types A and B NPD). To investigate the mechanisms underlying enzyme replacement therapy for this disorder, we studied the uptake of recombinant, human ASM (rhASM) by alveolar macrophages from ASM knock-out (ASMKO) mice. The recombinant enzyme used for these studies was produced in Chinese hamster ovary cells and contained complex type, N-linked oligosaccharides. Binding of radiolabeled, rhASM to the ASMKO macrophages was enhanced as compared with normal macrophages, consistent with their larger size and increased surface area. However, internalization of the enzyme by the ASMKO cells was markedly reduced when compared with normal cells. Studies using receptor-specific ligands to inhibit enzyme uptake revealed that in normal cells rhASM was taken up by a combination of mannose and mannose 6-phosphate receptors (MR and M6PR, respectively), whereas in the ASMKO cells the M6PR had a minimal role in rhASM uptake. Expression of M6PR mRNA was normal in the ASMKO cells, although Western blotting revealed more receptors in these cells when compared with normal. We therefore hypothesized that lipid accumulation in ASMKO macrophages led to abnormalities in M6PR trafficking and/or degradation, resulting in reduced enzyme uptake. Consistent with this hypothesis, we also found that, when rhASM was modified to expose terminal mannose residues and target mannose receptors, the uptake of this modified enzyme form by ASMKO cells was ϳ10-fold greater when compared with the "complex" type rhASM. These findings have important implications for NPD enzyme replacement therapy, particularly in the lung.Types A and B Niemann-Pick disease (NPD) 1 are lysosomal storage disorders resulting from an inherited deficiency of acid sphingomyelinase (ASM) activity (EC 3.1.4.12) (1). ASM is responsible for hydrolyzing the lipid, sphingomyelin, to ceramide and phosphocholine, and both forms of the disease are characterized by extensive lipid storage in various cells and tissues. Patients with Type A NPD follow a rapid, neurodegenerative course that leads to death by about 3 years of age, whereas Type B NPD patients have a less severe form of the disease with little or no neurological involvement. This latter form is characterized mainly by visceral organ complications, including hepatosplenomegaly and progressive pulmonary compromise (1, 2). Intermediate forms also have been described (e.g. Ref.3), revealing that ASM deficiency can lead to a wide spectrum of disease.Enzyme replacement therapy was first suggested as an approach for the treatment of lysosomal storage disorders over 30 years ago (4), although difficulties in purifying the human enzymes limited its early evaluation (5-7). However, during the past decade the isolation of genes encoding most lysosomal enzymes and the development of expression systems that produced large quantities of recombinant proteins led to the successful treatment of sev...

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“…The cells display oxidative burst and secrete many cytokines (e.g., IL-1, TNFbeta, IL-6). Importantly, the NR8383 cells express a functional mannose receptor (Lane et al 1998), an attribute not present in other macrophage cell lines such as HL60, U937, and RAW264. The mannose receptor is an important phagocytic and endocytic receptor critical for immune response and host defense.…”

Section: Rat Alveolar Macrophagesmentioning

confidence: 99%

“…The mannose receptor is an important phagocytic and endocytic receptor critical for immune response and host defense. The attributes of this cell line have been exploited in numerous studies of the health impacts of environmental particles (Riley et al 2005;Gazin et al 2004;Fach et al 2002;Lane et al 1998;Long et al 1997). Per ATCC protocol, cultures are maintained by transferring floating cells to additional flasks-the floating cells are functionally normal.…”

Section: Rat Alveolar Macrophagesmentioning

confidence: 99%

A Macrophage-Based Method for the Assessment of the Reactive Oxygen Species (ROS) Activity of Atmospheric Particulate Matter (PM) and Application to Routine (Daily-24 h) Aerosol Monitoring Studies

Landreman

Shafer

Hemming

et al. 2008

Aerosol Science and Technology

148

133

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Both short-and long-term exposure to particulate matter (PM) air pollution have been demonstrated to cause increases in cardiovascular disease, cancer, and respiratory disorders. Although the specific mechanisms by which exposure to PM cause these affects are unclear, significant evidence has accumulated to suggest that PM exposure leads to increased inflammation as the result of excessive production of reactive oxygen species (ROS) in critical cell types. In order to better understand how real-world PM exposure causes adverse health effects, there is a need to efficiently integrate metrics of PM toxicity into large scale air monitoring and health effects/epidemiology studies. Here we describe a rapid, inexpensive, method that can be employed to assess the potential of sub-mg masses of PM to generate oxidative stress in alveolar macrophage cells. Importantly, the approach is compatible with routine daily PM sampling programs such as those administered by EPA (Speciation trends network (STN), IMPROVE network, PM2.5 mass monitoring network), allowing for multiple samples to be assessed simultaneously with low volumes and brief exposure periods. We apply the method to a set of water extracts of daily PM2.5 samples (25-350 µg PM mass) collected in the Denver-Metro area. Variations in the magnitude of the ROS response observed between the samples were only partially explained by differences in mass loading, with the highest levels of ROS being observed in samples collected during the summer months. This assay provides a very useful tool that can be coupled with detailed chemical analysis and statistical models to work towards the goal of attributing PM toxicity to specific real-world chemical sources.

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Characterization of a rat alveolar macrophage cell line that expresses a functional mannose receptor

Cited by 41 publications

References 34 publications

Alveolar Macrophages Bind and Phagocytose Allergen- Containing Pollen Starch Granules Via C-Type Lectin and Integrin Receptors: Implications for Airway Inflammatory Disease

Alveolar Macrophages Bind and Phagocytose Allergen- Containing Pollen Starch Granules Via C-Type Lectin and Integrin Receptors: Implications for Airway Inflammatory Disease

Mannose 6-Phosphate Receptor-mediated Uptake Is Defective in Acid Sphingomyelinase-deficient Macrophages

A Macrophage-Based Method for the Assessment of the Reactive Oxygen Species (ROS) Activity of Atmospheric Particulate Matter (PM) and Application to Routine (Daily-24 h) Aerosol Monitoring Studies

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