bluuebunny/crossref_metadata_2025_split huggingface dataset:
Centrifugation attenuates the fluid shear response of circulating leukocytes
Authors: Fukuda Shunichi , Schmid-Schönbein Geert W 
Published: September 2022

AbstractHuman leukocytes retract pseudopods in response to physiological fluid shear, a phenomenon that serves to keep circulating leukocytes in a spherical state. We show here that leukocyte fluid shear response is attenuated irreversibly by centrifugation. Inhibition of shear response depends on duration and magnitude of acceleration during centrifugation and time duration after centrifugation. Even after low-speed centrifugation, leukocytes no longer retract pseudopods during shear application. After centrifugation at higher acceleration, leukocytes project pseudopods instead of retracting during shear application, which can be suppressed by a calcium channel blocker. We examined the role of fluid shear response in vivo by reintroduction of centrifuged cells into the rat circulation. Centrifuged leukocytes have a significantly enhanced tendency to migrate into tissue. These observations indicate that centrifugation may irreversibly damage the fluid shear response of leukocytes. It causes an impaired leukocyte behavior after reintroduction into the circulation, suggesting that shear response is a requirement for normal passage of leukocytes through the microcirculation.
Human monocyte scavenger receptors are pattern recognition receptors for (1→3)-β-D-glucans
Authors: Rice Peter J , Kelley Jim L , Kogan Grigorij , Ensley Harry E , Kalbfleisch John H , Browder I William , Williams David L 
Published: September 2022

AbstractGlucans are cell wall constituents of fungi and bacteria that bind to pattern recognition receptors and modulate innate immunity, in part, by macrophage activation. We used surface plasmon resonance to examine the binding of glucans, differing in fine structure and charge density, to scavenger receptors on membranes isolated from human monocyte U937 cells. Experiments were performed at 25°C using a biosensor surface with immobilized acetylated low density lipoprotein (AcLDL). Inhibition of the binding by polyinosinic acid, but not polycytidylic acid, confirmed the interaction of scavenger receptors. Competition studies showed that there are at least two AcLDL binding sites on human U937 cells. Glucan phosphate interacts with all sites, and the CM-glucans and laminarin interact with a subset of sites. Polymer charge has a dramatic effect on the affinity of glucans with macrophage scavenger receptors. However, it is also clear that human monocyte scavenger receptors recognize the basic glucan structure independent of charge.
Polysaccharide purified fromGanoderma luciduminhibits spontaneous and Fas-mediated apoptosis in human neutrophils through activation of the phosphatidylinositol 3 kinase/Akt signaling pathway
Authors: Hsu Ming-Jen , Lee Shiuh-Sheng , Lin Wan-Wan 
Published: September 2022

AbstractGanoderma lucidum has been widely used as a remedy to promote health and longevity in China. The polysaccharide component with a branched (1→3)-β-D-glucan moiety from G. lucidum (PS-G) has shown evidence of enhancement of immune responses and of eliciting anti-tumor effects. In this study, we investigated the effect of PS-G on neutrophil viability, which is manifested by spontaneous apoptosis. Annexin V staining and MTT assays reveal that PS-G is able to inhibit spontaneous and Fas-induced neutrophil apoptosis, and this effect of PS-G is enhanced by the presence of zVAD (a caspase inhibitor) and GM-CSF. The antiapoptotic effect of PS-G is diminished by the presence of wortmannin and LY294002 (two PI-3K inhibitors), but is not altered by PD98059 (a MEK inhibitor). Western blotting indicates the stimulating effect of PS-G on Akt phosphorylation and its inhibition of procaspase 3 degradation, which occurs in neutrophils undergoing spontaneous apoptosis or triggered death by Fas. Taken together, PS-G elicitation of antiapoptotic effects on neutrophils primarily relies on activation of Akt-regulated signaling pathways.
Numerical and functional alterations of circulating γδ T lymphocytes in aged people and centenarians
Authors: Argentati Katy , Re Francesca , Donnini Alessia , Tucci Maria G , Franceschi Claudio , Bartozzi Beatrice , Bernardini Giovanni , Provinciali Mauro 
Published: September 2022

AbstractThe aim of this study was to evaluate the peripheral representation, in vitro expansion, cytokine production, and cytotoxicity of γδ T lymphocytes from 104 healthy subjects ranging in age from 19 to 103 years. We demonstrated that the absolute number of circulating γδ+ T cells was reduced significantly in old people and centenarians in comparison with young subjects as a consequence of the age-related decreased lymphocyte number. The decrease was a result of an age-dependent reduction of Vδ2 T cells, whereas the absolute number of Vδ1 T cells was unaffected by age. As a consequence, the Vδ2/Vδ1 ratio was inverted in old subjects and centenarians. A higher percentage of γδ+ T cells producing tumor necrosis factor α was found in old donors and centenarians, whereas no age-related difference was observed in interferon -γ production. After a 10-day in vitro expansion, a twofold lower expansion index of γδ T cells, and particularly of a Vδ2, but not of a Vδ1 subset, was found in old people and centenarians in comparison with young subjects. The cytotoxicity of sorted γδ T cells was preserved in old people and centenarians. The alteration of γδ T cells could contribute to the age-related derangement of T cell-mediated, adoptive responses and may represent a new characteristic of immunosenescence.
Differential involvement of CD40, CD80, and major histocompatibility complex class I molecules in cytotoxicity induction and interferon-γ production by human natural killer effectors
Authors: Terrazzano Giuseppe , Zanzi Delia , Palomba Carmen , Carbone Ennio , Grimaldi Serena , Pisanti Simona , Fontana Silvia , Zappacosta Serafino , Ruggiero Giuseppina 
Published: September 2022

AbstractNatural killer (NK) cells are physiologically involved in the immune response against viruses, intracellular bacteria, and parasites as well as against malignant diseases. In addition to the cytotoxic activity, NK lymphocytes mediate a variety of homeostatic effects by producing cytokines. This study focused on the differential role of CD40 and CD80 costimulatory molecules and major histocompatibility complex class I (MHC-I) antigens in the regulation of cytotoxicity and of interferon (IFN)-γ secretion of resting and interleukin (IL)-2-activated human NK cells. CD40 and CD80 molecules were observed to play a specific role in the induction of cytotoxic function but not in IFN-γ production of IL-2-activated NK effectors. In addition, a critical role of CD94-dependent MHC-I recognition for the regulation of IFN-γ production and target lysis was demonstrated. These data provide a possible mechanism underlying functional interactions between NK lymphocytes and CD40/CD80-expressing cell targets, as represented by dendritic cells.
Leptin inhibits the anti-CD3-driven proliferation of peripheral blood T cells but enhances the production of proinflammatory cytokines
Authors: Lord Graham M , Matarese Giuseppe , Howard Jane K , Bloom Stephen R , Lechler Robert I 
Published: September 2022

AbstractThere is increasing evidence that leptin affects immune responses and that in the absence of leptin, immunity is suboptimal. Most data so far indicate that leptin increases proinflammatory immune responses by an effect on T cells and macrophages. Here we show that, under certain circumstances, leptin can inhibit T cell proliferative responses. Separation of the responding T cells into different subpopulations revealed an interesting heterogeneity of cellular behavior in that naïve and memory T cells were differentially affected by leptin. The anti-CD3-driven proliferation of memory T cells was inhibited by leptin, whereas that of naïve T cells was markedly enhanced. Despite the inhibition of proliferation of the memory T cells, their production of interferon-γ was substantially increased. These data show that leptin can inhibit certain immune responses in vitro. However, despite this inhibition of proliferation, the production of proinflammatory cytokines is significantly enhanced by leptin. The findings demonstrated here show further complexity in the actions of leptin on the immune system.
Scavenger receptor cysteine-rich domains 9 and 11 of WC1 are receptors for the WC1 counter receptor
Authors: Ahn J S , Konno A , Gebe J A , Aruffo A , Hamilton M J , Park Y H , Davis W C 
Published: September 2022

AbstractWorkshop cluster 1 (WC1) is a member of the scavenger receptor cysteine-rich (SRCR) superfamily that includes CD5, CD6, CD163, and M160. Bovine WC1 consists of 11 SRCR domains, a unique domain 1, and two homologous 5 SRCR domain cassettes, WC1 domains 2–6 and 7–11. The porcine orthologue of WC1 contains five SRCR domains with a different domain arrangement. Although the function of WC1 is unknown, WC1 is proposed to be an accessory or homing molecule. Thus, identification of cells that express the counter receptor for WC1 (WC1-CR) is critical to understanding the function of WC1. For this reason, we constructed WC1-human immunoglobulin G1 fusion proteins to identify the binding domain of WC1 and cells that express the WC1-CR. Immunohistochemical analysis revealed WC1 domains 9 and 11 bind cells with macrophage and dendritic cell morphology and cells in ellipsoids in the spleen. These results and the finding of conserved signaling motifs in the cytoplasmic tail suggest WC1 may be an accessory molecule.
CpG-DNA stimulates cellular and humoral immunity and promotes Th1 differentiation in aged BALB/c mice
Authors: Maletto Belkys , Rópolo Andrea , Morón Victor , Pistoresi-Palencia María Cristina 
Published: September 2022

AbstractWe examined whether CpG-DNA could be used as adjuvant to induce a T helper cell type-1 (Th1) immunity in aged BALB/c mice that showed a Th2 polarization. Bordetella pertussis and complete Freund's adjuvant (CFA) were used as well. Immunization with ovalbumin (OVA)/CpG-DNA showed that the immunoglobulin G (IgG)2a/IgG1 ratio and OVA-specific T cell response were similar in young and aged mice. OVA/CpG-DNA induced the secretion of interferon-γ (IFN-γ) and absence of interleukin (IL)-5. Similar results were found in mice immunized with OVA/CFA. When mice were immunized with OVA/B. pertussis, we found that the IgG2a/IgG1 ratio and OVA-specific T cell response were lower in aged mice and elicited IFN-γ and IL-5. In vitro CpG-DNA stimulated antigen-presenting cells to display IL-12 and up-regulate the expression of major histocompatibility complex class II and B7-2 on B cells as efficiently in aged as in young mice, but the up-regulation of B7-1 was stronger i aged mice. The findings demonstrate that CpG-DNA is able to induce a young-like Th1 specific immune response in aged mice.
Multiple signals are required for maturation of human dendritic cells mobilized in vivo with Flt3 ligand
Authors: Mosca Paul J , Hobeika Amy C , Colling Kirsten , Clay Timothy M , Thomas Elaine K , Caron Dania , Lyerly H Kim , Morse Michael A 
Published: September 2022

AbstractThe ligand for the receptor tyrosine kinase fms-like tyrosine kinase 3(Flt3L) is a growth factor for hematopoietic progenitors and inducesexpansion of the two distinct lineages of dendritic cells (DC) that have been described in humans. These two lineages, DC1 and DC2, have been described according to their ability to induce naive T celldifferentiation to T helper cell type 1 (Th1) and Th2 effector cells, respectively. The immunoregulatory potential of DC1 and DC2 depends on their state of maturation and activation, which can be mediated byseveral molecules. Because monocyte-derived DC1 produce interleukin-12(IL-12) when stimulated with CD40 ligand (CD40L), we hypothesized thatsimilar results would be obtained with DC1 mobilized by Flt3L. Unexpectedly, we found that immature DC expanded in vivo by Flt3Ltreatment could not be stimulated to produce IL-12 in vitro using CD40Land/or interferon-γ (IFN-γ) alone. Instead, we found that Flt3L-mobilized DC from cancer patients require a sequence of specificsignals for maturation, which included initial treatment withgranulocyte macrophage-colony stimulating factor followed by acombination of maturation signals such as CD40L and IFN-γ. Flt3L-mobilized DC matured in this manner possessed greater Tcell-stimulatory function than nonmatured DC. The ability to generatephenotypically mature, IL-12-producing DC1 from peripheral bloodmononuclear cells mobilized by Flt3L will have important implicationsfor the development of effective cancer immunotherapystrategies.
The mononuclear phagocyte system revisited
Authors: Hume David A , Ross Ian L , Himes S Roy , Sasmono R Tedjo , Wells Christine A , Ravasi Timothy 
Published: September 2022

AbstractThe mononuclear phagocyte system (MPS) was defined as a family of cells comprising bone marrow progenitors, blood monocytes, and tissue macrophages. In this review, we briefly consider markers for cells of this lineage in the mouse, especially the F4/80 surface antigen and the receptor for macrophage colony-stimulating factor. The concept of the MPS is challenged by evidence that there is a separate embryonic phagocyte lineage, the blurring of the boundaries between macrophages and other cells types arising from phenotypic plasticity and transdifferentiation, and evidence of local renewal of tissue macrophage populations as opposed to monocyte recruitment. Nevertheless, there is a unity to cells of the MPS suggested by their location, morphology, and shared markers. We discuss the origins of macrophage heterogeneity and argue that macrophages and antigen-representing dendritic cells are closely related and part of the MPS.
A role for endogenous IL-12 in tumor immunity: IL-12 is required for the acquisition of tumor-migratory capacity by T cells and the development of T cell-accepting capacity in tumor masses
Authors: Uekusa Yasuhiro , Gao Ping , Yamaguchi Nobuya , Tomura Michio , Mukai Takao , Nakajima Chigusa , Iwasaki Masayuki , Takeuchi Noritame , Tsujimura Takahiro , Nakazawa Mitsuhiro , Fujiwara Hiromi , Hamaoka Toshiyuki 
Published: September 2022

AbstractInterleukin (IL)-12 plays a central role in the initiation and regulation of T cell-mediated immune responses. The present study investigated how IL-12, endogenously produced during tumor vaccination, functions for anti-tumor immune responses. Mice were given anti-IL-12 monoclonal antibody during immunization with attenuated syngeneic tumor cells. Splenic T cells from anti-IL-12-treated immunized mice exhibited comparable levels of tumor-neutralizing activity with those from tumor-immunized mice without anti-IL-12 treatment. When these two groups of mice were directly challenged with viable tumor cells, tumor rejection was induced only in anti-IL-12-untreated mice. T cell infiltration was observed at the site of tumor challenge in these mice, whereas such a T cell infiltration did not occur in anti-IL-12-treated mice. The tumor-migratory capacity was directly assessed by transferring spleen cells from tumor-immunized mice into syngeneic, tumor-bearing recipient mice and by quantitating donor cells migrating into recipients’ tumor masses. T cells from anti-IL-12-treated tumor-immunized mice were found to exhibit a markedly reduced tumor-migratory capacity when compared with that of anti-IL-12-untreated mice. Moreover, the migration of T cells from anti-IL-12-untreated mice to tumor masses prepared in anti-IL-12-treated mice was severely reduced. These results indicate that endogenously produced IL-12 has dual roles in anti-tumor-immune resistance: One is to confer T cells with a tumor-migratory capacity, and the other is to allow tumor masses to develop the capacity to accept tumor-migrating T cells.
Induction of regulatory T cells by the immunomodulating cytokines α-melanocyte-stimulating hormone and transforming growth factor-β2
Authors: Namba Kenichi , Kitaichi Nobuyoshi , Nishida Tomomi , Taylor Andrew W 
Published: September 2022

AbstractRecently, we have reported that the cytokines α-melanocyte-stimulating hormone (α-MSH) and transforming growth factor-β2 (TGF-β2) work in synergy to induce the activation of regulatory T (Treg) cells. When we used α-MSH and TGF-β2 to generate ocular autoantigen-specific Treg cells and adoptively transferred them into mice susceptible to experimental autoimmune uveoretinitis (EAU), there was suppression in the incidence and severity of EAU. Specificity to a retinal autoantigen was required for the Treg cells to suppress EAU. When stimulated, these Treg cells produced TGF-β1, and their production of interferon-γ, interleukin (IL)-10, and IL-4 was suppressed. Also, the Treg cells are suppressed in their proliferative response. Our results demonstrate that α-MSH with TGF-β2 induce Treg cells that can subdue a tissue-specific autoimmune response. This also promotes the possibility of using these immunomodulating cytokines to purposely induce antigen-specific Treg cells to prevent and suppress autoimmune disease.
Secretion of interleukin-10 or interleukin-12 by LPS-activated dendritic cells is critically dependent on time of stimulus relative to initiation of purified DC culture
Authors: Jiang Hui-Rong , Muckersie Elizabeth , Robertson Marie , Xu Heping , Liversidge Janet , Forrester John V 
Published: September 2022

AbstractDendritic cells (DC) are key regulators of adaptive immunity with the potential to induce T cell activation/immunity or T cell suppression/tolerance. DC are themselves induced by “maturation” signals such as bacterial lipopolysaccharide (LPS). We demonstrate here that LPS can stimulate DC to display similar maturation phenotypes but to differentiate toward an interleukin (IL)-10high- or IL-12high-secretor profile depending on the timing of maturation signal induction. Immediate/early administration of LPS induced purified bone marrow-derived DC (BMDC) to differentiate as IL-10highIL-12low-secreting cells, termed early DC (eDC). Conversely, delayed administration of LPS altered the DC cytokine profile to IL-10lowIL-12high, termed later DC (lDC). The presence of IL-4 enhanced the yield and maturation of BMDC but inhibited LPS-induced IL-10 production by eDC. In contrast, interferon-γ reduced the yield of DC but promoted the level of LPS-induced IL-10 production by lDC. Our data provide new evidence that ex vivo manipulation and the cytokine environment regulate DC maturation status and cytokine-secretor phenotype with implications for the control of T cell differentiation and function via DC-based immunotherapeutic strategies.
Acute mast cell-dependent neutrophil recruitment in the skin is mediated by KC and LFA-1: inhibitory mechanisms of dexamethasone
Authors: Schramm Rene , Schaefer Thilo , Menger Michael D , Thorlacius Henrik 
Published: September 2022

AbstractThis study examined adhesive and signaling pathways and anti-inflammatory mechanisms of dexamethasone in acute mast cell-dependent neutrophil recruitment in the skin in mice. Mast cell activation dose- and time-dependently triggered influx of predominately neutrophils and secretion of cytokine-induced neutrophil chemoattractant (KC). Neutralization of KC attenuated neutrophil recruitment upon mast cell activation. Mast cell activation- and KC-induced neutrophil responses were significantly decreased in lymphocyte function-associated antigen-1 (LFA-1)-deficient mice. Dexamethasone inhibited neutrophil accumulation elicited by mast cell activation. It is interesting that dexamethasone significantly reduced the mast cell-dependent secretion of KC, whereas neutrophil recruitment induced by exogenous KC was insensitive to dexamethasone treatment. Thus, KC is a fundamental mediator of neutrophil recruitment in acute mast cell-dependent skin inflammation, and mast cell activation- and KC-induced neutrophil responses are LFA-1-dependent. Moreover, dexamethasone inhibits mast cell-regulated skin infiltration of neutrophils mainly by attenuating KC secretion. Thus, this study elucidates important interactions between chemokines and adhesion molecules in mast cell-dependent neutrophil recruitment and provides new insight into mechanisms of dexamethasone in skin inflammation.
Involvement of CD44 in leukocyte trafficking at the blood-retinal barrier
Authors: Xu Heping , Manivannan Ayyakkannu , Liversidge Janet , Sharp Peter F , Forrester John V , Crane Isabel J 
Published: September 2022

AbstractIn the present study, we investigated the involvement of CD44 in leukocyte trafficking in vivo at the blood-retinal barrier using experimental autoimmune uveoretinitis (EAU) as a model system. Leukocyte trafficking was evaluated using adoptive transfer of calcein-AM (C-AM)-labeled spleen cells harvested from syngeneic mice at prepeak severity of EAU to mice at a similar stage of disease. CD44 and its ligand hyaluronan were up-regulated in the eye during EAU. CD44-positive leukocytes were found sticking in the retinal venules and postcapillary venules but not in the retinal arterioles nor in mesenteric vessels. Preincubation of in vitro C-AM-labeled leukocytes with anti-CD44 monoclonal antibodies (mAb; IM7) or high molecular weight hyaluronic acid (HA) before transfer significantly suppressed leukocyte rolling but not sticking in retinal venules and also reduced cell infiltration in the retinal parenchyma. Administration of the HA-specific enzyme hyaluronidase to mice before cell transfer also reduced leukocyte infiltration, suggesting that CD44-HA interactions are involved in leukocyte recruitment in EAU. This was further supported by the observation that disease severity was reduced by administration of anti-CD44 mAb (IM7) at the early leukocyte-infiltration stage. Further studies also indicated that CD44 activation was associated with increased levels of apoptosis, and this may also be in part responsible for the reduction in disease severity. These findings demonstrate that CD44 is directly involved in leukocyte-endothelial interaction in vivo and influence the trafficking of primed leukocytes to the retina and their overall survival.
Functional cross-talk between cytokine receptors revealed by activating mutations in the extracellular domain of the β-subunit of the GM-CSF receptor
Authors: Blake Timothy J , Jenkins Brendan J , D'Andrea Richard J , Gonda Thomas J 
Published: September 2022

AbstractSeveral reports have suggested an interaction between the erythropoietin receptor (EpoR) and the shared signaling subunit (hβc) of the human granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 receptors, although the functional consequences of this interaction are unclear. We previously showed that in vivo expression of constitutively active extracellular (EC) mutants of hβc induces erythrocytosis and Epo independence of erythroid colony-forming units (CFU-E). This occurs despite an apparent requirement of these mutants for the GM-CSF receptor α-subunit (GMRα), which is not expressed in CFU-E. Here, we show that coexpression of hβc EC mutants and EpoR in BaF-B03 cells, which lack GMRα, results in factor-independent proliferation and JAK2 activation. Mutant receptors that cannot activate JAK2 fail to produce a functional interaction. As there is no detectable phosphorylation of hβc on intracellular tyrosine residues, EpoR displays constitutive tyrosine phosphorylation. These observations suggest that JAK2 activation mediates cross-talk between EC mutants of hβc and EpoR. The implications of these data are discussed as are our findings that activated hβc mutants can functionally interact with certain other cytokine receptors.