bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elimination, blocking, and activation of macrophages: three of a kind?
Authors: van Rooijen Nico , Sanders Annemarie 
Published: January 2018

Abstract
In mammals, macrophages are multifunctional cells. Apart from their scavenger role in the clearance of nonself materials such as microorganisms and altered-self materials such as apoptotic cells, senescent erythrocytes, immune complexes, and inflammatory products, they play a crucial role in the regulation of both innate and acquired immunity. Whereas the former activity is based on phagocytosis and intracellular degradation, the latter activity largely depends on the production and secretion of a panel of regulatory molecules such as cytokines, chemokines, and nitrogen oxide (NO). Depletion of macrophages and blocking of phagocytosis form important approaches to study the role of these cells in various host defense mechanisms. Moreover, the efficacy of drug-and gene-targeting, based on the application of particulate carrier devices, can be improved in this way. However, compounds originally described as efficacious blockers of phagocytosis simultaneously activate their production of cytokines and NO. Moreover, elimination, blocking, as well as activation of macrophages are all dependent on the concentration of such compounds. When administered in vivo, they will reach some macrophages in a high and others in a low concentration. As a consequence, the former cells may be eliminated or blocked, whereas the latter are activated by the same treatment. In this review, the various methods for suppression of macrophage functions are compared and requirements for the development of new, selective, and organ-specific macrophage-suppressing devices are discussed.
Dietary fish oil diminishes the antigen presentation activity of rat dendritic cells
Authors: Sanderson Peter , MacPherson G Gordon , Jenkins Chris H , Calder Philip C 
Published: January 2018

Abstract
Rats were fed for 6 weeks on a low fat (LF) diet or on high fat diets containing safflower oil [SO; rich in n-6 polyunsaturated fatty acids (PUFAs)] or fish oil (FO; rich in n-3 PUFAs). Lymph-borne dendritic cells (L-DC) were isolated after cannulation of the thoracic duct and were used as antigen [keyhole limpet hemocyanin (KLH)] -presenting cells in an ex vivo assay that used KLH-sensitized spleen lymphocytes as the responder cells. FO feeding significantly diminished the antigen presentation activity of L-DC compared with L-DC from rats fed each of the other diets. The antigen presentation activity of L-DC from rats fed the SO diet was greater than that of L-DC from rats fed the LF diet. Feeding the FO diet significantly reduced both the proportion of CD2-positive L-DC and the level of CD2 expression on L-DC compared with feeding each of the other diets; the proportions of L-DC staining positive for CD40, CD18, CD54, CD11a, and MHC II were unaffected by diet. However, FO feeding reduced the level of expression of CD18, CD11a, MHC II, and CD54 on L-DC compared with feeding the other two diets; the level of expression of CD40 was unaffected by diet. This is the first study to report effects of dietary fatty acids on dendritic cells. The suppressive effect of FO feeding may account for some of the beneficial effects of n-3 polyunsaturated fatty acids observed in clinical settings, such as prolonged survival of grafts and diminished chronic inflammatory responses. However, such an effect may also be detrimental because host defense toward bacterial and other antigens could be compromised.
Induction and modulation of macrophage Ia antigen expression by platelet-activating factor
Authors: Erickson Kent L , Howard Angela D , Hubbard Neil E 
Published: January 2018

Abstract
Expression of major histocompatibility complex class II molecules, Ia, can be significantly augmented by interferon-γ (IFN-γ) in macrophages. In this study we demonstrate that platelet-activating factor (PAF) was also a potent inducer of Ia antigen expression on macrophages. PAF-induced Ia expression was both time- and dose-dependent. Maximal Ia expression was induced with 25 nM PAF after 3-h exposure to PAF. Ia expression in macrophages stimulated with PAF for 24 h was not significantly greater than unstimulated macrophages. Treatment of macrophages with IFN-γ and PAF did not affect either the kinetics or concentration required for maximal Ia expression induced by either IFN-γ or PAF. PAF-induced Ia expression was inhibited by the specific PAF receptor antagonists, WEB 2086, Ro 24-0238, and Ro 24-4637, indicating a receptor-mediated event Like IFN-γ-induced Ia expression, PAF activity was inhibited by prostaglandin E2 (PGE2). However, that expression was only inhibited after 24 h when macrophages were treated with the PGE2 synthesis inhibitors, flurbiprofen and indomethacin. These findings demonstrate that PAF, along with its role as a potent proinflammatory mediator, was also capable of inducing Ia expression on macrophages through the PAF receptor and that expression was altered by PGE2.
Effect of serine proteinase inhibitors on neutrophil function: α-1-proteinase inhibitor, antichymotrypsin, and a recombinant hybrid mutant of antichymotrypsin (LEX032) modulate neutrophil adhesion interactions
Authors: Carney David F , Jagels Mark A , Hugli Tony E , Sands Howard , Rubin Harvey 
Published: January 2018

Abstract
Circulating serine proteinase inhibitors (serpins) regulate a number of proteinases that participate in the inflammatory process. In this study, we investigated possible modulatory effects of serpins on neutrophil adhesion. Antichymotrypsin (ACT), α1-protease inhibitor (α1-PI), and LEX032, a recombinant hybrid of ACT and α1-PI were shown to inhibit neutrophil adhesion to fibronectin (FN)-coated surfaces and, to a lesser extent, adhesion to other extracellular matrix proteins. The inhibitory effect of serpins on neutrophil adhesion to FN was found to be related to inhibition of FN proteolysis based on the following observations: (1) elastase treatment of FN-coated plates, but not of neutrophils, resulted in enhanced neutrophil adhesion; and (2) serpins inhibited FN proteolysis by neutrophil proteases. Serpins also inhibited neutrophil spreading, as well as shedding of neutrophil CD43, but not L-selectin, CD18, or CD29. We conclude that serpins modulate neutrophil adhesion both by inhibiting proteolytic processing of extracellular matrix proteins and proteolytic shedding of CD43.
Anti-HIV-1 activity of indolicidin, an antimicrobial peptide from neutrophils
Authors: Robinson W Edward , McDougall Brenda , Tran Dat , Selsted Michael E 
Published: January 2018

Abstract
Indolicidin is a tridecapeptide amide isolated from the cytoplasmic granules of bovine neutrophils. It has potent, broad spectrum microbicidal activities in vitro that are thought to be related to the membrane-disruptive properties of the peptide. Based on the putative membrane-targeted mode of action, we postulated that indolicidin would be active against HIV-1, an enveloped virus. Indolicidin was reproducibly virucidal against HIV-1 at a concentration of 333 μg/mL (174 μM) with a 50% inhibitory dose between 67 and 100 μg/mL. At 37°, killing was rapid with &gt;50% killing of HIV occurring within 5 min, and nearly 100% viral inactivation achieved by 60 min. The anti-HIV activity of indolicidin was temperature-sensitive, a finding consistent with a membrane-mediated antiviral mechanism. Parallel experiments revealed that indolicidin lysed cultured lymphoblastoid cells at concentrations similar to those required for antiviral activity. However, a des-R13-amide indolicidin analog (R12-OH), previously shown to have less antibacterial activity than indolicidin, was significantly less active against HIV and was non-toxic to lymphoid target cells at concentrations up to 333 μg/mL, the highest level tested.
Treatment of mice with anti-CD44 after allogeneic bone marrow cell transplantation is lethal
Authors: Zöller Margot , Föhr Nicole , Herrmann Karin 
Published: January 2018

Abstract
Because CD44 is known to be of functional importance in hematopoiesis, we were interested in whether anti-CD44 would interfere with syngeneic or allogeneic bone marrow cell engraftment. Syngeneic and allogeneic grafts were accepted by over 80% of mice. In both the syngeneic and the allogeneic host, homing, repopulation, and regain of immunoreactivity was delayed by anti-CD44 treatment. But in the syngeneic host the overall survival rate was unaltered. Instead, less than 25% of anti-CD44-treated, allogeneically reconstituted mice survived by recovery of the host's hematopoietic system, i.e. graft acceptance was close to 0%. The mice died between 4 and 15 days after engraftment and showed severe alterations of the gut. The high death rate of the allogeneically reconstituted mice was specific for anti-CD44 treatment. It did not depend on an ADCC mechanism, could not be abrogated by depletion of T cells, and was only mitigated by depletion of NK cells. According to the histological appearance of the gut, anti-CD44 strengthens a local (gut-associated) graft versus host reaction, which is not mediated by αβ T cells and at least not exclusively by NK cells. Because gut death is one of the major reasons for failure in allogeneic bone marrow transplantation, the model of anti-CD44-induced lethality offers itself to clarify the underlying mechanism.
The invasive and destructive behavior of HIV-induced T cell syncytia on collagen and endothelium
Authors: Sylwester Andrew , Daniels Karla , Soll David R 
Published: January 2018

Abstract
HIV-induced syncytia of the CD4+ SUP-T1 T cell line mimic the subcellular organization of single cells and are able to crawl like single cells through extension of giant pseudopods. Because syncytia have been demonstrated in lymphoid tissue of HIV-positive individuals, their behavior has been investigated on more natural substrata, including dehydrated collagen, hydrated collagen, endothelial monolayers, and endothelial monolayers grown on collagen cushions. On hydrated collagen gels, both individual SUPT1 cells and syncytia form unusually long cylindrical projections that possess pseudopodial ends and are highly dynamic. Syncytia penetrate collagen gels through extension of these projections and disrupt their integrity. When incubated on endothelium, both single cells and syncytia readily traverse the monolayer through holes, and when incubated on endothelium supported by a collagen cushion, syncytia generate large holes through the monolayer, penetrate the monolayer, and disrupt the collagen gel through extension of long, complex projections. Invading syncytia also release viruses in a polarized fashion which adhere to and are taken up in vesicles by the endothelium. It is suggested that the destructive behaviors of syncytia which have been demonstrated in vitro may have correlates in vivo.
CSF-1 (M-CSF) differentially sensitizes mononuclear phagocyte subpopulations to endotoxin in vivo: a potential pathway that regulates the severity of Gram-negative infections
Authors: Chapoval Andrei I , Kamdar Sonya J , Kremlev Sergey G , Evans Robert 
Published: January 2018

Abstract
CSF-1 is known to prime mononuclear phagocytes (MNP) for inflammatory stimuli in vitro. We hypothesized that CSF-1 in vivo can sensitize the host to the increased production of endotoxic shock mediators such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6). Indeed, when CSF-1-primed mice were challenged with lipopolysaccharide (LPS), increased levels of serum IL-6 and TNF-α were detected. Both intravenous and intraperitoneal injections of CSF-1 resulted in increased sensitivity to LPS challenge, which induced maximum increases in serum IL-6 when administered via the intraperitoneal route. The peak serum IL-6 production in control and CSF-1-primed mice occurred 2–3 h after LPS injection, whereas that of TNF-α occurred by 1–2 h. When peripheral blood leukocytes, spleen cells, and resident peritoneal cells (PC) were isolated from CSF-1-primed mice injected with LPS, only the PC were shown to release IL-6 constitutively and none released TNF-α. A comparison of mRNA isolated from various cells and tissues after intraperitoneal CSF-1 priming indicated that only PC expressed IL-6 mRNA, whereas PC, liver, and spleen expressed TNF-α mRNA. All tissues showed increased levels of IL-6 and TNF-α mRNA in response to LPS challenge. Only liver and kidney showed an enhanced level of IL-6 expression in CSF-1-primed mice challenged with LPS, whereas liver, lung, and kidney showed enhanced TNF-α expression. These data indicate that CSF-1 primes tissue MNP but not circulating MNP to transcribe mRNA and release IL-6 and TNF-α. Overall, the data suggest that CSF-1 plays an important role in regulating the sensitivity of the host to the pathophysiological effects of endotoxin.
Effect of proteasome inhibitors on monocytic IκB-α and -β depletion, NF-κB activation, and cytokine production
Authors: Haas Monika , Page Sharon , Page Michael , Neumann Franz-Josef , Marx Nikolaus , Adam Michaela , Ziegler-Heitbrock H W Löms , Neumeier Dieter , Brand Korbinian 
Published: January 2018

Abstract
We investigated the effect of proteasome inhibitors on the lipopolysaccharide (LPS)-induced expression of several monocytic cytokines, which may be dependent on the transcription factor, nuclear factor-κB (NF-κB). Exposure of human monocytic THP-1 cells to ALLN and Mu873 prevented the LPS-induced degradation of IκB-α and -β, as did the more potent proteasome inhibitor, PSI, whereas several calpain inhibitors were ineffective. This was accompanied by the inhibition of nuclear NF-κB binding activity and NF-κB transcriptional activation. At the mRNA level, the inhibitors blocked the expression of tumor necrosis factor (TNF) and interleukin-1β (IL-1β), whereas IL-8 remained unaffected by ALLN and was only partially reduced by the highest dose of PSI. The latter effect appears to be due to an increase in IL-8 mRNA stability in the presence of proteasome inhibitors. Furthermore, the production of TNF was efficiently suppressed by ALLN and PSI, less by Mu873, and not at all by calpain inhibitors. In primary human blood monocytes ALLN also prevented the LPS-induced degradation of IκB-α and -β, efficiently blocked the production of TNF and, to a lesser extent, IL-1β, whereas that of IL-8 was not inhibited. The expression of NF-κB-dependent monocytic cytokines may be selectively controlled by the proteasome, offering a potential therapeutic target in inflammatory disease.
Platelets induce monocyte differentiation in serum-free coculture
Authors: Ammon C , Kreutz M , Rehli M , Krause S W , Andreesen R 
Published: January 2018

Abstract
Terminal maturation of blood monocytes (MO) in vitro and in vivo into macrophages (MAC) occurs as a result of interactions with various cell types. To characterize some of the cell-cell connections that maybe important for MO differentiation we cocultured human MO with lymphocytes and/or with platelets. We found that intact platelets strongly promoted MO maturation under serum-free conditions as evident from the expression of differentiation-dependent antigens and morphology. To further characterize the differentiation-inducing component(s) we prepared membrane and cytosol fractions of platelets. Both fractions could induce MO maturation, comparable to intact platelets. Further centrifugation of the cytosolic fraction revealed that only the pellet of ultracentrifugation, e.g., membrane fragments, could induce MO differentiation. Digestion with either trypsin or neuraminidase could only partially inhibit this effect. The same was true for heat-treated fractions, indicating that this platelet-derived differentiation stimulus is not solely an intact protein. Next we prepared protein and lipid fractions of platelets. Treatment of MO with platelet proteins or platelet lipids clearly showed that only the lipid components were able to induce MO maturation. We propose components present in the lipid fraction of platelet membranes as possible inducers of MO maturation in vitro.
Specific Th1 cell lines that confer protective immunity against experimental Borrelia burgdorferi infection in mice
Authors: Pride Michael W , Brown Eric L , Stephens L Clifton , Killion Jerald J , Norris Steven J , Kripke Margaret L 
Published: January 2018

Abstract
Although humoral responses to Borrelia burgdorferi (Bb) have been shown to be protective in some animal models of Lyme disease, the role of T cells in this disease is less well understood. This work describes three Bb-specific T cell lines that prevent disease progression in syngeneic mice. The T cell lines were generated in C3H mice immunized with Bb in complete Freund's adjuvant. All lines were Bb-specific, CD4+, TCRαβ+, and they proliferated and produced interferon-γ and interleukin-2 on stimulation with Bb. Injection of the cell lines into naive C3H recipients significantly reduced the number of organisms recoverable from the blood and tissues of infected mice and protected them from developing Bb-induced periarthritis. These studies demonstrated that Th1 cells can confer resistance to Bb infection in susceptible mice and suggested that the timing of this T cell response may be critical for determining disease outcome.
Neuropeptide regulation of proinflammatory cytokine responses
Authors: Dickerson Camille , Undem Bradley , Bullock Brandon , Winchurch Richard A 
Published: January 2018

Abstract
Severe traumatic injuries and infections are frequently accompanied by life-threatening shock and are associated with increases in the proinflammatory cytokines, particularly tumor necrosis factor α (TNF-α). The body's first perception of injury is the nociceptive or pain response. This response is induced at the site of injury and is transmitted systemically by sensory neuropeptides, the tachykinins, released from sensory afferent c-fiber neurons. We studied the role of tachykinins in regulating the production of proinflammatory cytokines induced by the administration of bacterial lipopolysaccharide. Destruction of terminal sensory nerve endings before lipopolysaccharide administration abrogates tachykinin synthesis and down-regulates TNF-α transcription and secretion. In contrast, the responses of interleukins-1 and -6 are unaffected. Pretreating animals with an antagonist for the substance P-specific NK-1 receptor also down-regulated the TNF-α response, whereas blockade of the NK-2 receptor had no effect. These findings indicate that substance P contributes to the induction of those cytokines that are involved in precipitating the shock response.
Interleukin-2 induces development of dendritic cells from cord blood CD34+ cells
Authors: Bykovskaja Svetlana N , Buffo Mary Jo , Bunker Mark , Zhang Haifan , Majors Alana , Herbert Mary , Lokshin Anna , Levitt Mark L , Jaja Andrew , Scalise Deborah , Kosiban Deborah , Evans Carol , Marks Stanley , Shogan Jeffrey 
Published: January 2018

Abstract
Dendritic cells (DC) have been shown to develop along a myeloid or lymphoid lineage of differentiation propagated from bone marrow or early thymic precursor cells with hematopoietic cytokines. In our study, we have induced growth and differentiation of DC from cord blood CD34+ cells initiated in interleukin-2 (IL-2) alone or in IL-2 + stem cell factor (SCF) + tumor necrosis factor α (TNF-α)-supplemented medium and cultured with IL-2 or IL-2 + SCF for 28–35 days. Dendritic morphology and antigenic phenotype of DC grown with IL-2 were characteristic for DC cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Growth and differentiation of DC was followed by an increase in expression of MHC II and co-stimulating molecules CD80 and CD86. We have also shown the expression of the IL-2 receptor (IL-2R) γ-chain in CD34+ cells after 2–3 days of culture with IL-2 alone. The co-expression of the IL-2R α, β, and γ subunits in both DC cultured with IL-2- or GM-CSF-containing cocktail of cytokines was also shown. The time curve for induction of IL-2R demonstrated low levels of subunit expression at the beginning of culture. The number of CD1a cells coexpressing CD25, CD122, and CDγ increased to about 24–68 and to 78–95% after 21 and 28–35 days, respectively. Development of natural killer cells was shown along with DC. The proportion of CD56+ cells and cytotoxicity increased in a time-dependent manner.
Overview of interleukin-18: more than an interferon-γ inducing factor
Authors: Dinarello Charles A , Novick Daniela , Puren Adrian J , Fantuzzi Giamila , Shapiro Leland , Mühl Heiko , Yoon Do-Young , Reznikov Leonid L , Kim Soo-Hyun , Rubinstein Menachem 
Published: January 2018

Abstract
Initially described in 1989 as interferon-γ (IFN-γ) inducing factor (IGIF), interleukin-18 (IL-18) is a novel proinflammatory cytokine that is clearly more than an inducer of IFN-γ The cytokine possesses several biological properties such as activation of nuclear factor-κB (NF-κB), Fas ligand expression, the induction of both CC and CXC chemokines, and increased production of competent human immunodeficiency virus. Most activities are due to a receptor complex that recruits the IL-1 receptor-activating kinase (IRAK), leading to translocation of NF-κB. This property and others support the concept that IL-18 is related to the IL-1 family. Indeed, one of the IL-18 receptor chains is the IL-1 receptor-related protein, a member of the IL-1R family. In addition, IL-18 is structurally similar to IL-1β and like IL-1β is first synthesized as a leaderless precursor requiring the IL-1β converting enzyme for cleavage into an active molecule. The biology of IL-18 is reviewed in the overview and the implication for a role for this cytokine in disease is presented.
T cell development and activation in Jak3-deficient mice
Authors: Baird Allison M , Thomis Daniel C , Berg Leslie J 
Published: January 2018

Abstract
Jak3, a member of the Janus family of tyrosine kinases, participates in signaling through cytokine receptors that contain the common γ-chain, including the receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15. Jak3- and γc-deficient mice have pleiotropic defects that can be attributed to their inability to respond to multiple specific cytokines. A great deal of recent work has focused on the T cell defects in these mutant mice. Specifically, Jak3- and γc-deficient mice have small thymuses revealing a defect in T cell development, and in addition, have functionally unresponsive peripheral T cells with an activated/memory cell phenotype. The thymic defect in these mutant mice strongly resembles that seen in IL-7 and IL-7 receptor knockout mice, suggesting that the lack of IL-7 receptor signaling accounts for this defect in Jak3-/- and γc– mice. To characterize this defect further, we have examined the earliest stages of T cell development in adult and fetal Jak3-/- thymuses. These studies identify two discrete developmental defects at the CD4–CD8– stage of T cell maturation. Analyses of peripheral T cells in Jak3-/-and γc– mice have also revealed a number of abnormalities. All of the T cells in these mutant mice have an activated phenotype and a large fraction of them are proliferating in vivo. In addition, Jak3-/- and γc– T cells are more prone to undergo apoptosis than wild-type T cells. Together, these features account for the decreased IL-2 secretion by in vitro-stimulated Jak3-/- T cells. Overall, many of the lymphoid defects of Jak3- and γc-deficient mice can be accounted for by the lack of IL-7R and IL-2R signaling; however, other cytokine systems must also be involved in maintaining peripheral T cell homeostasis.