Journal of Leukocyte Biology

Our medical research library holds 7 studies published in Journal of Leukocyte Biology (1988–2015). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 7 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Oxford University Press
• Published: 1984 to the present, England
• Language: English
• ISSN: 0741-5400 (print), 1938-3673 (electronic)
• Continues: Reticuloendothelial Society. RES. Journal of the Reticuloendothelial Society
• Its record in the NLM Catalog

2010s

• Neutrophil elastase promotes myofibroblast differentiation in lung fibrosis. A.D. Gregory, C.R. Kliment, H.E. Metz, et al. 2015;98(2):143-52. PubMed · Publisher · Free full text

  Abstract

  IPF is a progressive lung disorder characterized by fibroblast proliferation and myofibroblast differentiation. Although neutrophil accumulation within IPF lungs has been negatively correlated with outcomes, the role played by neutrophils in lung fibrosis remains poorly understood. We have demonstrated previously that NE promotes lung cancer cell proliferation and hypothesized that it may have a similar effect on fibroblasts. In the current study, we show that NE(-/-) mice are protected from asbestos-induced lung fibrosis. NE(-/-) mice displayed reduced fibroblast and myofibroblast content when compared with controls. NE directly both lung fibroblast proliferation and myofibroblast differentiation in vitro, as evidenced by proliferation assays, collagen gel contractility assays, and αSMA induction. Furthermore, αSMA induction occurs in a TGF-β-independent fashion. Treatment of asbestos-recipient mice with ONO-5046, a synthetic NE antagonist, reduced hydroxyproline content. Thus, the current study points to a key role for neutrophils and NE in the progression of lung fibrosis. Lastly, the study lends rationale to use of NE-inhibitory approaches as a novel therapeutic strategy for patients with lung fibrosis.

  © Society for Leukocyte Biology.

• The role of inflammasome-derived IL-1 in driving IL-17 responses. K.H. Mills, L.S. Dungan, S.A. Jones, et al. 2013;93(4):489-97. Review PubMed · Publisher

  Abstract

  NLRs are members of the PRR family that sense microbial pathogens and mediate host innate immune responses to infection. Certain NLRs can assemble into a multiprotein complex called the inflammasome, which activates casapse-1 required for the cleavage of immature forms of IL-1β and IL-18 into active, mature cytokines. The inflammasome is activated by conserved, exogenous molecules from microbes and nonmicrobial molecules, such as asbestos, alum, or silica, as well as by endogenous danger signals, such as ATP, amyloid-β, and sodium urate crystals. Activation of the inflammasome is a critical event triggering IL-1-driven inflammation and is central to the pathology of autoinflammatory diseases, such as gout and MWS. Recent studies have also shown IL-1 or IL-18, in synergy with IL-23, can promote IL-17-prduction from Th17 cells and γδ T cells, and this process can be regulated by autophagy. IL-1-driven IL-17 production plays a critical role in host protective immunity to infection with fungi, bacteria, and certain viruses. However, Th17 cells and IL-17-seceting γδ T cells, activated by inflammasome-derived IL-1 or IL-18, have major pathogenic roles in many autoimmune diseases. Consequently, inflammasomes are now major drug targets for many autoimmune and chronic inflammatory diseases, as well as autoinflammatory diseases.

1990s

• Alveolar macrophage kinetics and multinucleated giant cell formation after lung injury. H. Prieditis, I.Y. Adamson. 1996;59(4):534-8. PubMed · Publisher

  Abstract

  Multinucleated giant cells (MGC) are a prominent feature of some chronic inflammatory states in the lung. These cells are formed by macrophage fusion, but how this process relates to the kinetics of alveolar macrophage (AM) production and proliferation is not clear. In this serial study, we compare AM kinetics and MGC formation after instilling carbon, silica, asbestos, bleomycin, and saline into the lungs of mice. Animals were killed up to 16 weeks later with [3H]thymidine injected 1 h before death. Counts of AM and MGC were carried out after bronchoalveolar lavage, and cell labeling was assessed by autoradiography. All test substances induced an inflammatory response with equal AM numbers recovered up to 2 weeks. Subsequently, the number returned to normal after carbon but remained elevated in the other groups. After carbon the lung structure was normal, there was no increase in AM label, and no MGC formed. Bleomycin-injected lungs progressed to fibrosis with only a brief, small increase in AM labeling and no MGC formation. After silica, and particularly asbestos, the lungs showed fibrosis, and many granulomas with large MGC were seen. Lavaged AM from these lungs showed a significant increase in DNA synthesis after 2 weeks, followed by higher numbers of MGC, none of which were labeled. Labeled AM tended to be free of particles, whereas MGC after 4 weeks contained many particles. The results indicate a relationship between AM proliferation and fusion, whereby AM growth appears to be prerequisite for cell infusion and MGC formation as a feature of granulomatous disease.

• Asbestos-induced injury to cultured human pulmonary epithelial-like cells: role of neutrophil elastase. D.W. Kamp, M. Dunne, M.S. Dykewicz, et al. 1993;54(1):73-80. PubMed · Publisher

  Abstract

  The mechanisms responsible for asbestos-induced pulmonary epithelial cell cytotoxicity, especially oxidant-independent mechanisms, are not established. We determined whether human polymorphonuclear leukocyte (PMN) proteases contribute to asbestos-induced damage to human pulmonary epithelial-like cells (PECs) assessed using an in vitro chromium-51 release assay. Serine antiproteases, phenylmethylsulfonyl fluoride and alpha 1-antitrypsin, each ameliorated PEC injury induced by amosite asbestos and PMNs. A role for a specific proteinase, human neutrophil elastase (HNE), is supported by the facts that (1) asbestos increased HNE release assessed by an enzyme-linked immunosorbent assay technique (1.7 +/- 0.5 vs. 2.8 +/- 0.5 micrograms/ml; P < .025), (2) purified HNE or porcine pancreatic elastase (PPE) each alone caused PEC detachment, (3) asbestos plus either HNE or PPE caused PEC lysis similar to that mediated by asbestos and PMNs, and (4) cationic agents released from PMNs were unlikely to be involved because polyanions did not ameliorate injury resulting from asbestos and PMNs. Compared to elastase, cathepsin G caused less PEC detachment and negligible augmentation in asbestos-induced PEC lysis. Asbestos increased the association of 125I-labeled elastase with PECs nearly 50-fold compared with PPE alone (14.4% vs. 0.3%, respectively; P < .01) and nearly 10-fold compared with another particle, opsonized zymosan. We conclude that PMN-derived proteases, especially elastase, may contribute to asbestos-induced lung damage by augmenting pulmonary epithelial cell injury.

• Bidirectional modulation of TNF-alpha production by alveolar macrophages in asbestos-induced pulmonary fibrosis. S. Ouellet, H. Yang, R.A. Aubin, et al. 1993;53(3):279-86. PubMed · Publisher

  Abstract

  Bronchoalveolar lavage (BAL) cells were isolated from rats 1, 3, and 6 weeks after a single intratracheal instillation of saline, UICC chrysotile asbestos (5 mg), or silica (5 mg). In asbestos-exposed rats, the pulmonary response was characterized by a significant increase in the number of alveolar macrophages (AMs) and the appearance of fibrotic lesions within 1 week. By contrast, mixed macrophage and neutrophil accumulations were observed in the silica group without evidence of fibrosis. Tumor necrosis factor-alpha (TNF-alpha) production by lipopolysaccharide (LPS)-stimulated BAL cells from asbestos-treated rats was significantly lower than controls 1 and 3 weeks after exposure. However, by 6 weeks higher levels of TNF-alpha production were noticeable in this group. Decreases in LPS-induced TNF-alpha production were also observed with BAL cells from silica-treated animals at all time points studied. Lower levels of TNF-alpha were not related to decreased BAL cell viability or the presence of a significant proportion of neutrophils in the silica group. Furthermore, biphasic changes in TNF-alpha production seen in the asbestos group were correlated with concomitant decreases (3 weeks) and increases (6 weeks) in levels of TNF-alpha mRNA in AMs. These data indicate that lower levels of TNF-alpha resulted from inhibition at the gene expression level and provide evidence for bidirectional modulation of TNF-alpha production by AMs during inflammatory reactions.

• Inhibition of alveolar macrophage cytotoxicity by asbestos: possible role of prostaglandins. E. Bissonnette, B. Carré, C. Dubois, et al. 1990;47(2):129-34. PubMed · Publisher

  Abstract

  Asbestosis and silicosis are chronic, fibrosing lung diseases due to prolonged inhalation of asbestos fibers or silica particles. However, little is known about the implication of these toxic dusts on cell-mediated cytotoxicity. Among the first types of cells that are in contact with the dusts are the alveolar macrophages (AM). We studied the effect of different concentrations of UICC chrysotile asbestos and silica on 18-h cytotoxicity of AM against tumor necrosis factor (TNF)-resistant P815 target cells or TNF-sensitive L929 target cells. Rat AM, obtained by bronchoalveolar lavage, were incubated for 2 h with 20, 50, or 100 micrograms/ml chrysotile or silica before the addition of target cells. AM cytotoxicity was significantly inhibited at greater than 20 micrograms/ml of chrysotile. In contrast, silica did not inhibit AM-mediated cytotoxicity at any concentration used. Asbestos, but not silica, caused significant production of PGE2 by macrophages and target cells. Addition of the cyclooxygenase inhibitor indomethacin to our system abolished all inhibition by asbestos. These results suggest that the inhibition of AM-mediated cytotoxicity by chrysotile was caused by prostaglandins, and that fibrogenic particles differ in their capacity to modulate AM function.

1980s

• Lung exposure to mineral dusts enhances the capacity of lung inflammatory cells to release superoxide. A. Cantin, F. Dubois, R. Bégin. 1988;43(4):299-303. PubMed · Publisher

  Abstract

  In vitro exposure of macrophages and neutrophils to inorganic dusts can enhance their oxidative metabolism, however the effects of inorganic dust inhalation on lung-inflammatory cell-oxidative metabolism remain unknown. To address this issue, we studied the superoxide anion release from lung inflammatory cells obtained by bronchoalveolar lavage from 19 sheep exposed repeatedly to UICC chrysotile B asbestos (100 mg) over an 18 month period and 10 sheep exposed to a single exposure of quartz (100 mg) over a 6 month period. Exposure to asbestos and quartz did not induce an increase in the spontaneous release of superoxide from inflammatory cells. However lung-inflammatory cells from sheep exposed to asbestos released much higher levels of superoxide in the presence of phorbol myristate acetate (PMA) than did cells of unexposed sheep. In quartz exposed animals, superoxide release with PMA stimulation remained significantly increased up to 2 months after a single quartz infusion. These results suggest that inorganic dust inhalation primes lung inflammatory cells in vivo and markedly enhances their capacity to release toxic oxygen radicals.

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