Heat-shock protein synthesis by human polymorphonuclear cells.

Eid, Nemr; Kravath, Richard E.; Lanks, Karl W.

doi:10.1084/jem.165.5.1448

Cited by 43 publications

(13 citation statements)

References 14 publications

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“…A more difficult question is how these cytoplasts, fresh or preserved, kill bacteria as well as they do, and especially the CKP, which lacks both granules and activatable oxidase activity, both of which are thought necessary for optimal killing of catalase-positive organisms such as staphylococci (19 (22).…”

Section: Discussionmentioning

confidence: 99%

Cryopreservable neutrophil surrogates. Stored cytoplasts from human polymorphonuclear leukocytes retain chemotactic, phagocytic, and microbicidal function.

Malawista¹,

Blaricom²,

Breitenstein³

1989

J. Clin. Invest.

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Cryopreservation of polymorphonuclear leukocytes (PMN) has largely failed, probably because of their rich content of granular (lysosomal) enzymes. We have been developing granule-poor cytoplasts (anucleate fragments) from PMN which retain motile functions of the parent cell. The two types studied here were induced either by brief heating on surfaces (cytokineplasts) or by discontinuous gradient centrifugation (Ficoll) without heat or drugs (U-cytoplasts). Freshly made, these cytoplasts respond chemotactically to formyl peptide (fMetLeu-Phe), and they take up and kill roughly half as many Staphylococcus aureus as their (larger, granular) parent PMN. Unlike their parent cells, after cryopreservation both cytoplasts remain chemotactic, and in matched experiments they take up and kill staphylococci with undiminished avidity. These findings are the first indications that PMN cytoplasts suitable for clinical use may be feasible.

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Section: Discussionmentioning

confidence: 99%

Cryopreservable neutrophil surrogates. Stored cytoplasts from human polymorphonuclear leukocytes retain chemotactic, phagocytic, and microbicidal function.

Malawista¹,

Blaricom²,

Breitenstein³

1989

J. Clin. Invest.

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“…Cassatella et al (10) reported that the effect of IFN-y on PMN superoxide generation could be blocked by actinomycin D, suggesting a transcriptional control mechanism for at least some components of the PMN response. Other evidence for gene regulation (by unknown control mechanisms) in PMN includes the findings that the level of c-fos oncogene transcripts rises upon stimulation of PMN by chemotactic oligopeptides (46) and that heat shock proteins, which are generally subject to transcriptional control, are inducible by heat treatment of PMN (47). Regulation of mRNA levels for a gene responsible for phagocytic function, such as phagocytic cytochrome b heavy chain, has not previously been directly demonstrated in mature granulocytes.…”

Section: Ifn-y Response In Monocytic Leukemiamentioning

confidence: 99%

Induction of phagocyte cytochrome b heavy chain gene expression by interferon gamma.

Newburger

Ezekowitz

Whitney

et al. 1988

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

123

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Phagocytic cells, such as macrophages and polymorphonuclear leukocytes, produce a "respiratory burst" in which oxygen is reduced to superoxide and other active oxygen species responsible for many of the microbicidal, tumoricidal, and inflammatory activities of these cells. Interferon y has been shown to augment phagocyte superoxide production, but the molecular mechanisms underlying this effect have remained unknown. Recently a key component of the oxidase, phagocyte cytochrome b, has been characterized as a heterodimer of a 91-kDa glycoprotein and a 22-kDa polypeptide. The present studies examined the effects of human recombinant interferon y on the expression of the genes for these components of the cytochrome b. In vitro treatment with interferon y substantially increases the level of phagocyte cytochrome b heavy chain gene transcripts in normal polymorphonuclear leukocytes, normal monocyte-derived macrophages, and the monocytic leukemia cell line THP-1. Light chain gene transcripts are less affected. In monocyte-derived macrophages and THP-1 cells, the enhanced expression of the heavy chain gene appears in large part attributable to increased rates of transcription. Treatment of monocyte-derived macrophages with human recombinant interferon a (a downregulator of the respiratory burst) decreased the heavy chain transcript levels; interferon 1 produced no detectable change.These findings demonstrate the responsiveness of one essential component of the phagocyte oxidase system to activation by interferon y and provide a rationale for its use to augment phagocytic function in chronic granulomatous disease.

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“…36,37 For glucose deprivation, cells were incubated in IMDM without D-glucose or sodium pyruvate (Gibco Life Technologies, Paisley, Scotland).…”

Section: Neutrophil Isolation and Culturementioning

confidence: 99%

Involvement of a ferroprotein sensor in hypoxia-mediated inhibition of neutrophil apoptosis

Mecklenburgh

Walmsley

Cowburn

et al. 2002

Blood

103

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Neutrophil apoptosis represents a major mechanism involved in the resolution of acute inflammation. In contrast to the effect of hypoxia observed in many other cell types, oxygen deprivation, as we have shown, causes a profound but reversible delay in the rate of constitutive apoptosis in human neutrophils when aged in vitro. This effect was mimicked by exposing cells to 2 structurally unrelated ironchelating agents, desferrioxamine (DFO) and hydroxypyridines (CP-94), and it appeared specific for hypoxia in that no modulation of apoptosis was observed with mitochondrial electron transport inhibitors, glucose deprivation, or heat shock. The involvement of chelatable iron in the oxygen-sensing mechanism was confirmed by the abolition of the DFO and CP-94 survival effect by Fe 2؉ ions. Although hypoxia inducible factor-1␣ (HIF-1␣) mRNA was identified in freshly isolated neutrophils, HIF-1␣ protein was only detected in neutrophils incubated under hypoxic conditions or in the presence of DFO. Moreover, studies with cyclohexamide demonstrated that the survival effect of hypoxia was fully dependent on continuing protein synthesis. These results indicate that the neutrophil has a ferroprotein oxygen-sensing mechanism identical to that for erythropoietin regulation and results in HIF-1␣ up-regulation and profound but reversible inhibition of neutrophil apoptosis. This finding may have important implications for the resolution of granulocytic inflammation at sites of low-oxygen tension. IntroductionNeutrophils are key effector cells of the innate immune system and play a vital role in host defense against gram-negative bacteria. However, excessive or sustained activation of these cells can result in significant tissue damage, with injury resulting from the release of histotoxic granule contents, reactive-oxygen intermediates, and other proinflammatory mediators. 1 Persistent accumulation of primed and activated neutrophils is a cardinal feature of a number of lung diseases, including acute lung injury, bronchiectasis, and chronic obstructive airways disease, and it is associated with disease progression and destruction of lung tissue. 2 Similarly, in myocardial infarction, neutrophils have been implicated in extending the area of primary myocardial injury by releasing protease-rich granule contents into adjacent viable tissue, 3 and, in rheumatoid arthritis, neutrophil-derived reactive-oxygen species and granule enzymes have been demonstrated in synovial fluid and again implicated in disease pathogenesis. 4,5 Understanding the mechanisms that modulate neutrophil influx, activation, and longevity is therefore of major pathophysiologic importance to a number of organ systems. The latter 2 events are regulated in large part by the capacity of senescent neutrophils to undergo spontaneous apoptosis, which leads to inhibition of secretory function and to prompt ingestion and removal by inflammatory macrophages. 6,7 Apoptosis is a constitutive event in neutrophils and is proposed to be a major mechanism underlying the resolutio...

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Heat-shock protein synthesis by human polymorphonuclear cells.

Cited by 43 publications

References 14 publications

Cryopreservable neutrophil surrogates. Stored cytoplasts from human polymorphonuclear leukocytes retain chemotactic, phagocytic, and microbicidal function.

Cryopreservable neutrophil surrogates. Stored cytoplasts from human polymorphonuclear leukocytes retain chemotactic, phagocytic, and microbicidal function.

Induction of phagocyte cytochrome b heavy chain gene expression by interferon gamma.

Involvement of a ferroprotein sensor in hypoxia-mediated inhibition of neutrophil apoptosis

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