Alpha-1-antitrypsin in human macrophages.

Isaacson, Peter G.; Jones, David B.; Millward-Sadler, G. H.; Judd, M.; Payne, Sandra V.

doi:10.1136/jcp.34.9.982

Cited by 157 publications

(38 citation statements)

References 14 publications

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“…These observations are consistent with the finding by Andersen (43,44) that neutrophils produce alAT and the findings of others that noted lymphocytes and fibroblasts do not (40,42). Furthermore, the observation of Rogers et al (28) that unfractionated blood leukocytes express a1AT mRNA, but less than the liver, is consistent with the concept that not only do blood monocytes express a IAT but that neutrophils do as well.…”

Section: Northern Analysissupporting

confidence: 82%

“…The different Pi phenotypes were not associated with any difference in the release of these control proteins. Furthermore, when the cells were labeled for 24 h, scanning of the autoradiogram ofthe secreted a 1AT demonstrated that PiZZ alveolar macrophages secreted 10-fold less alAT than PiMM alveolar macrophages ( (37)(38)(39)(40), and that rat alveolar macrophages synthesize alAT (41) as do normal human blood monocytes (27,(42)(43)(44)46). Furthermore, Budek et al (45) have shown that when rat lung mRNA is translated in vitro in a rabbit reticulocyte system, a lAT is produced, and Perlmutter et al (27,46) have recently demonstrated alAT mRNA transcripts in normal human monocytes, alyeolar macrophages, and breast milk macrophages with characteristics similar to those that we observed.…”

Section: Northern Analysismentioning

confidence: 99%

“…As a result, the three carbohydrate side chains added in the rough endoplasmic reticulum to asparaginyl residues at positions 46, 83, and 247 are not trimmed appropriately, leaving high-mannose carbohydrates attached to the Z protein that accumulates in the rough endoplasmic reticulum (4,15,16,36). In addition to the hepatocytes, it is also known that cells of the mononuclear series, including monocytes, alveolar macrophages, and breast milk macrophages all produce a lAT (27,(37)(38)(39)(40)(41)(42)(43)(44)(45)(46). Because the level of alAT produced by these cells is thought to be quite low, mononuclear phagocytes have been generally ignored as playing a relevant role in the normal physiology of a lAT or in the pathogenesis ofthe decreased amounts of c lAT found in the PiZZ form of a lAT deficiency.…”

Section: Introductionmentioning

confidence: 99%

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Expression of the alpha-1-antitrypsin gene in mononuclear phagocytes of normal and alpha-1-antitrypsin-deficient individuals.

Mornex¹,

Chytil-Weir²,

Martinet³

et al. 1986

J. Clin. Invest.

166

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To evaluate the contribution of mononuclear phagocytes, and particularly alveolar macrophages, to alpha-l-antitrypsin (alAT) production in normal and alAT-deficient individuals, Northern analysis with a human alAT complementary DNA was used to demonstrate that alAT messenger RNA (mRNA) can be detected in liver, blood monocytes, and alveolar macrophages.Quantification of alAT mRNA expression demonstrated that: (a) type PiMM monocytes and alveolar macrophages expressed, respectively, 200-fold and 70-fold less alAT mRNA per cell than the liver, (b) the level of expression of the alAT gene was increased during the in vitro maturation of blood monocytes; and (c) blood monocyte and alveolar macrophage levels of expression of the alAT gene were the same in PiMM and PiZZ individuals. However, the amount of newly synthesized alAT secreted by ZZ alveolar macrophages was 10 times lower than that secreted by MM alveolar macrophages. Thus, mononuclear phagocytes of PiZZ individuals express a secretory defect in alAT in a fashion similar to hepatocytes. Not only do mononuclear phagocytes provide a readily accessible cell to evaluate the regulation of alAT gene expression, but these cells may contribute to the levels of alAT present in the lower respiratory tract in the nornul and ZZ states.

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Section: Northern Analysissupporting

confidence: 82%

Section: Northern Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Expression of the alpha-1-antitrypsin gene in mononuclear phagocytes of normal and alpha-1-antitrypsin-deficient individuals.

Mornex¹,

Chytil-Weir²,

Martinet³

et al. 1986

J. Clin. Invest.

166

View full text Add to dashboard Cite

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“…Both proteins are serine proteinase inhibitors produced by various tumor cells. While AAT is primarily secreted by the liver [23], it is also secreted by monocytes and certain types of tumors [24][25][26], and is associated with inflammation, infection and other malignant diseases. Its C-terminal fragment can potentiate proliferation, invasiveness and NF-κB (nuclear factor kappa B) activity in breast cancer cells [27].…”

Section: Validation Of the Lc-ms Datamentioning

confidence: 99%

Identification of Differentially Secreted Biomarkers Using LC-MS/MS in Isogenic Cell Lines Representing a Progression of Breast Cancer

et al. 2007

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Proteins secreted (the secretome) from cancer cells are potentially useful as biomarkers of the disease. Using LC-MS/MS, the secreted proteomes from a series of isogenic breast cancer cell lines varying in aggressiveness were analyzed by mass spectrometry: non-tumorigenic MCF10A, premalignant/ tumorigenic MCF10AT, tumorigenic/locally invasive MCF10 DCIS.com and tumorigenic/ metastatic MCF 10CA cl. D. Proteomes were obtained from conditioned serum-free media, partially fractionated using a small reverse phase C2 column and digested with trypsin for analysis by LC-MS/MS, using a method previously shown to give highly enriched secreted proteomes (Mbeunkui, et. al., J. Prot. Res. 5, 899-906 2006). The search files produced from 5 analyses (3 separate preparations) were combined for database searching (Mascot) which produced a list of over 250 proteins from each cell line. The aim was to discover highly secreted proteins which changed significantly in abundance corresponding with aggressiveness. The most apparent changes were observed for alpha-1-antichymotrypsin and galectin-3-binding protein which were highly secreted proteins from MCF10 DCIS.com and MCF10CA cl. D, yet undetected in the MCF10A and MCF10AT cell lines. Other proteins showing increasing abundance in the more aggressive cell lines included alpha-1-antitrypsin, cathepsin D and lysyl oxidase. The S100 proteins, often associated with metastasis, showed variable changes in abundance. While the cytosolic proteins were low (e.g. actin and tubulin), there was significant secretion of proteins often associated with the cytoplasm. These proteins were all predicted as products of non-classical secretion (SecretomeIP, Center for Biological Sequence Analysis). The LC-MS/MS results were verified for five selected proteins by western blot analysis, and the relevance of other significant proteins is discussed. Comparisons with two other aggressive breast cancer cell lines are included and the protein with consistent association with aggressiveness in all lines, and in unrelated cancer cells, was the galectin-3-binding protein which has been associated with breast, prostate and colon cancer earlier, supporting the approach and findings. This analysis of an isogenic series of cell lines suggests the potential usefulness of the secretome for identifying prospective markers for the early detection and aggressiveness/progression of cancer.

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“…Hyaline droplets in rat renal tissue were tested for the presence of several proteins: cross-reactive antihuman lysozyme (Dakopatts, High Wycombe, Buckinghamshire) and anti-rat a,-antitrypsin (Seralab, Crawley Down, Sussex) as histiocytic markers (18,19), anti-rat a,,-globulin (courtesy of Dr. J. R.-F@ter), anti-rat Ig (Sera-lab), and cross-reactive anti-human albdmin (Dakopatts). In the mouse, the series included anti-mouse Ig (Sera-lab) instead of anti-rat Ig and excluded a,,-globulin.…”

Section: Iinintt Nohistocheinistrymentioning

confidence: 99%

Hyaline Droplet Accumulation in Rodent Kidney Proximal Tubules: An Association with Histiocytic Sarcoma

Hard

Snowden

1991

Toxicol Pathol

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A B S T R A~ Since recognition during the last decade that certain renal carcinogens can initially cause an accumulation of hyaline (protein) droplets in proximal tubules of male rats, it has become appropriate to establish whether this phenomenon of protein overload can also occur in rodent kidneys unrelated to chemical treatment. Kidney tissue from a number of selected rodent studies held in the National Toxicology Program (NTP) or Food and Drug Administration (FDA) archives were evaluated for hyaline droplet accumulation in proximal tubules. The survey concentrated on rats and mice of both sexes bearing hematopoietic tumors, as our preliminary observations had suggested this direction of study. The tissues of 101 Sprague-Dawley, 25 Osborne-Mendel, and 70 Fischer 344 rats and 96 B6C3F1 mice were examined. These animals provided an assortment of tumors including histiocytic sarcoma, lymphocytic lymphoma, mononuclear cell leukemia, and sarcoma. Hyaline droplet accumulation, primarily involving the P2 segment of proximal tubules, was diagnosed in 96% of rats with histiocytic sarcoma (74177 cases in Sprague-Dawley, 17/18 in Osborne-Mendels, 7/7 in Fischers) and in 55% of B6C3F1 mice with histiocytic sarcoma (18133 cases). There appeared to be a qualitative correlation between hyaline droplet accumulation and degree of tumor burden. Thus, in cases negative for hyaline droplets, the tumor was often confined to a single location, while increasing involvement of proximal segments beyond P2 occurred with more extensive multi-organ dissemination of the tumor. By immunohistochemistry on 11 cases of rat and 8 cases of mouse histiocytic sarcoma, the protein in hyaline droplets was identified as lysozyme, a known major secretory product of monocytes and macrophages. The hyaline droplets were negative for a,-antitrypsin, a,,-globulin, rat or mouse immunoglobulin, and albumin. More sparsely scattered droplets and granules present in proximal tubules of Fischer rats with mononuclear cell leukemia were negative for lysozyme but positive for either iron or lipofuscin pigment. The study establishes a clear association between renal tubule hyaline droplet and lysozyme accumulation in rats and mice with histiocytic sarcoma. Hyaline droplets secondary to neoplasia should be distinguished from chemically-induced hyaline droplet nephropathy in the male rat involving a,,-globulin.

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Alpha-1-antitrypsin in human macrophages.

Cited by 157 publications

References 14 publications

Expression of the alpha-1-antitrypsin gene in mononuclear phagocytes of normal and alpha-1-antitrypsin-deficient individuals.

Expression of the alpha-1-antitrypsin gene in mononuclear phagocytes of normal and alpha-1-antitrypsin-deficient individuals.

Identification of Differentially Secreted Biomarkers Using LC-MS/MS in Isogenic Cell Lines Representing a Progression of Breast Cancer

Hyaline Droplet Accumulation in Rodent Kidney Proximal Tubules: An Association with Histiocytic Sarcoma

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