bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dendritic cells and the pathogenesis of rheumatoid arthritis
Authors: Thomas Ranjeny , MacDonald Kelli PA , Pettit Allison R , Cavanagh Lois L , Padmanabha Jagdish , Zehntner Simone 
Published: January 2018

Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease in which unknown arthrogenic autoantigen is presented to CD4+ T cells. The strong association of the disease with an epitope within the HLA-DR chain shared between various alleles of HLA-DR4 and DR1 emphasizes the importance of antigen presentation. This immune response predominantly occurs in the synovial tissue and fluid of the joints and autoreactive T cells are readily demonstrable in both the synovial compartment and blood. Circulating dendritic cells (DC) are phenotypically and functionally identical with normal peripheral blood (PB) DC. In the synovial tissue, fully differentiated perivascular DC are found in close association with T cells and with B cell follicles, sometimes containing follicular DC. These perivascular DC migrate across the activated endothelium from blood and receive differentiative signals within the joint from monocyte-derived cytokines and CD40-ligand+ T cells. In the SF, DC manifest an intermediate phenotype, similar to that of monocyte-derived DC in vitro. Like a delayed-type hypersensitivity response, the rheumatoid synovium represents an effector site. DC at many effector sites have a characteristic pattern of infiltration and differentiation. It is important to note that the effector response is not self-limiting in RA autoimmune inflammation. In this article, we argue that the presentation of self-antigen by DC and by autoantibody-producing B cells is critical for the perpetuation of the autoimmune response. Permanently arresting this ongoing immune response with either pharmaceutical agents or immunotherapy is a major challenge for immunology. J. Leukoc. Biol. 66: 286–292; 1999.
Peripheral blood allogeneic microchimerism in lung and cardiac allograft recipients
Authors: Reinsmoen Nancy L , Jackson Annette , Hertz Marshall , Savik Kay , Kubo Spencer , Ormaza Sophia , Miller Leslie , McSherry Cynthia 
Published: January 2018

Abstract
We have been investigating two parameters, donor antigen-specific hyporeactivity and peripheral blood allogeneic microchimerism, to determine whether these parameters will predict a chronic rejection-free state and which recipients may be candidates for steroid withdrawal. We have identified donor antigen-specific hyporeactivity for 33% (16/48) of lung and 23% (11/47) of heart recipients. For both organ groups, the hyporeactive subgroup experienced a lower incidence of chronic rejection. The probability of donor antigen-specific hyporeactivity predicting a chronic rejection-free state is 100% for lung and 91% for heart recipients. We have identified peripheral blood allogeneic microchimerism for 77% (20/26) of lung and 36% (9/25) of heart recipients tested at 12–18 months posttransplant. Donor antigen-specific hyporeactivity correlates with a critical level of donor cells in lung recipients; the probability of high peripheral blood allogeneic microchimerism levels predicting a chronic rejection-free state in lung recipients is 100%. The results in heart recipients are not as clear with a short-, but not long-term, trend of higher chimerism levels correlating with the development of donor antigen-specific hyporeactivity. These results illustrate the usefulness of immune parameters to predict long-term graft outcome in an organ-specific manner. J. Leukoc. Biol. 66: 306–309; 1999.
Delayed clearance of apoptotic lymphoma cells allows cross-presentation of intracellular antigens by mature dendritic cells
Authors: Rovere Patrizia , Sabbadini Maria Grazia , Vallinoto Cristina , Fascio Umberto , Zimmermann Valerie S , Bondanza Attilio , Ricciardi-Castagnoli Paola , Manfredi Angelo A 
Published: January 2018

Abstract
Single cells are deleted from the midst of living tissue during normal turnover and embryogenesis. This event is not associated with inflammation or autoimmunity. Little is known of the clearance of apoptotic cells during dangerous situations, accompanied by extensive cell death and tissue damage: when macrophages are overwhelmed by apoptotic cells, other phagocytes, including immature dendritic cells (DCs), may become involved. DCs efficiently present antigens derived from the processing of internalized apoptotic bodies to class I- and class II-restricted T cells. Antigen presentation results either in T cell activation or in their functional blockade. The outcome is influenced by pro-inflammatory maturative signals: efficient T cell cross-priming requires fully mature DCs. Here we discuss in vitro data suggesting that the number of apoptotic cells that die at a given time influences DC maturation and therefore their ability to uptake antigens from apoptotic cells and cross-activate T lymphocytes. J. Leukoc. Biol. 66: 345–349; 1999.
A novel family of Ig-like receptors for HLA class I molecules that modulate function of lymphoid and myeloid cells
Authors: Colonna Marco , Nakajima Hideo , Navarro Francisco , López-Botet Miguel 
Published: January 2018

Abstract
We review what is presently known about structure, cellular distribution, biochemical characteristics, and function of a new family of human cell-surface receptors referred to as immunoglobulin-like transcripts (ILTs), leukocyte Ig-like receptors (LIRs), or monocyte/macrophage Ig-like receptors (MIRs). These receptors are genetically, structurally, and functionally related to a group of natural killer (NK) cell receptors for HLA class I molecules known as killer cell Ig-like receptors (KIRs). Distinct ILT/LIR/MIR isotypes are differentially expressed on lymphocytes, monocytes, macrophages, dendritic cells, and granulocytes; at least some of them recognize HLA class I molecules. Whereas some isotypes either inhibit or induce cell activation, others may be secreted as soluble receptors. ILT/LIR/MIR receptors may allow all immune cells to monitor class I expression on other cells and to respond in its absence, just as NK cells do. In addition, they may contribute to homeostasis by establishing activation thresholds that can be overcome only by relevant triggering stimuli and not by bystander cells. J. Leukoc. Biol. 66: 375–381; 1999.
Synovial PMN show a coordinated up-regulation of CD66 molecules
Authors: Hönig M , Peter H H , Jantscheff P , Grunert F 
Published: January 2018

Abstract
Changes in the expression of various activation-dependent surface markers have been reported for polymorphonuclear neutrophils (PMN) isolated from synovial fluid of patients with inflammatory joint diseases. We extend these findings to the expression of CD66 molecules and several other surface markers. Three members of the CD66 family, namely CD66a, CD66b, and CD66c, showed an up to fourfold up-regulation on synovial fluid PMN compared with peripheral blood PMN (PBG) of the same patients; CD59 was increased twofold, the expression of CD16 did not change, whereas CD62L was reduced by more than 50% on synovial fluid PMN. It is interesting that CD66a, CD66b, and CD66c showed a coordinated expression on PBG of patients and controls and a coordinated up-regulation on synovial neutrophils. In contrast, after in vitro stimulation of peripheral blood PMN with phorbol myristate acetate, CD66c was much less up-regulated compared with CD66a and CD66b. All samples of synovial fluid PMN exhibited an additional increase in the expression of CD66a, CD66b, and CD66c when stimulated with phorbol myristate acetate in vitro. Prostaglandins are known to inhibit various responses of neutrophils to inflammatory stimuli. We could show that prostaglandins inhibit N-formyl-methionyl-leucyl-phenylalanine-induced up-regulation of CD66 on peripheral blood PMN in a concentration-dependent manner. J. Leukoc. Biol. 66: 429–436; 1999.
Functional coupling and differential regulation of the Phospholipase A2-cyclooxygenase pathways in inflammation
Authors: Scott Kieran F , Bryant Katherine J , Bidgood Matthew J 
Published: January 2018

Abstract
Prostaglandins generated by the phospholipase A2 (PLA2)/cyclooxygenase (COX) pathway are well known to mediate diverse intracellular and extracellular effects that regulate mammalian development, vascular function, renal physiology, parturition, and immune responses to infection or wounding. In immune-mediated diseases and in certain cancers, this pathway is aberrantly upregulated and excessive prostaglandin production contributes to the pathology. It is now known that there are two isoforms of COX and multiple secreted and intracellular PLA2 enzymes. The use of isoform-specific inhibitors, coupled with antisense and in vivo gene deletion experiments, has identified independent pathways of arachidonic acid metabolism, which are differentially regulated at the levels of gene expression, protein phosphorylation, and cellular localization. There is cross-talk between the pathways at the level of PLA2 and substrate supply to the two isoforms of COX is apparently compartmentalized. Knockout studies have shown that the two COX isoforms play independent roles in immediate and delayed agonist- induced prostaglandin synthesis. Cytosolic PLA2-α is essential for both responses. Inducible secreted forms of PLA2 are, as yet, not essential for either response with the exception of the in vitro murine mast cell immediate response and instances of murine macrophage prostaglandin synthesis. These enzymes amplify the delayed response and are likely to modulate the severity of immune-mediated diseases. J. Leukoc. Biol. 66: 535–541; 1999.
Expression of serum amyloid A3 mRNA by inflammatory macrophages exposed to membrane glycoconjugates from Trypanosoma cruzi
Authors: Ferreira Ludmila R P , Silva Aristóbolo M , Michailowsky Vladimir , Reis Luiz F L , Gazzinelli Ricardo T 
Published: January 2018

Abstract
Differential display reverse transcriptase-polymerase chain reaction (PCR) was used to identify genes expressed by murine macrophages exposed to glycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from Trypanosoma cruzi trypomastigotes. Among the different PCR product bands identified in the differential display gel, one showed high homology with the serum amyloid A3 protein (SAA3). Northern blot assays showed augmentation of SAA3 mRNA expression by inflammatory macrophages exposed to live trypomastigotes or parasite glycolipids as compared to unstimulated macrophages. Our results also showed the expression of SAA3 mRNA, in liver and heart from animals in the acute phase of Chagas disease. It is important that expression of SAA3 mRNA was closely associated with tissue parasitism and presence of inflammatory cells. Together, our findings indicate the possible involvement of SAA3 protein on immunopathology of Chagas disease and establish a new infectious disease model to study the pathophysiological role of this acute-phase protein. J. Leukoc. Biol. 66: 593–600; 1999.
Morphine promotes apoptosis in Jurkat cells
Authors: Singhal Pravin C , Kapasi Aditi A , Reddy Krishna , Franki Nicholas , Gibbons Nora , Ding Guohua 
Published: January 2018

Abstract
Patients with intravenous heroin addiction are prone to recurrent infections and at times these infections are fatal. We evaluated the effect of morphine on the apoptosis of Jurkat cells and freshly isolated human T lymphocytes. Morphine promoted apoptosis of both the Jurkat cells and the freshly isolated T lymphocytes in a dose-dependent manner. DAGO, a specific p receptor agonist, also promoted Jurkat cell apoptosis. DNA isolated from morphine-treated Jurkat cells and T lymphocytes also showed integer multiples of 200 base pairs. Superoxide dismutase (SOD) enhanced lymphocyte apoptosis; whereas catalase attenuated the morphine-induced apoptosis of Jurkat cells as well as of T lymphocytes. Morphine-treated Jurkat cells also showed a decreased expression of bcl-2 and an enhanced expression of bax. In addition, morphine-treated Jurkat cells showed activation of caspase-3. These results indicate that morphine-induced T lymphocyte apoptosis may be mediated through the generation of reactive oxygen species. The change in ratio of bax and bcl-2 seems to tilt the balance toward apoptosis, leading to the activation of caspase-3. This study provides further support for the hypothesis that morphine may be directly compromising immune function by enhancing apoptosis of T lymphocytes in patients with heroin addiction. J. Leukoc. Biol. 66: 650–658; 1999.
Inhibitory and activating receptors involved in immune surveillance by human NK and myeloid cells
Authors: Colonna Marco , Nakajima Hideo , Cella Marina 
Published: January 2018

Abstract
We review the structure, cellular distribution, ligand specificity, and function of two emerging types of receptors involved in natural killer (NK) and myeloid cell recognition of other cells: ILT/LIR/MIR and 2B4 receptors. ILT/LIR/MIR receptors are differentially expressed on lymphoid and myeloid cells and two of them, ILT2 and ILT4, recognize HLA class I molecules. Whereas some receptors inhibit, others induce cell activation. 2B4 is broadly expressed on leukocytes, binds CD48, and mediates non-MHC-restricted cytotoxicity by NK cells. J. Leukoc. Biol. 66: 718–722; 1999.
The peroxisome proliferator-activated receptorγ (PPARγ) as a regulator of monocyte/macrophage function
Authors: Ricote Mercedes , Huang Jannet T , Welch John S , Glass Christopher K 
Published: January 2018

Abstract
Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors of the nuclear hormone receptor superfamily, which includes the steroid, retinoid, and thyroid hormone receptors. The PPARs can be activated by fatty acids and their eicosanoid metabolites, and have until recently been considered primarily to regulate genes involved in glucose and lipid homeostasis. In the past year there has been an explosive increase in research implicating PPARγ in macrophage biology, cell cycle regulation, and atherosclerosis. This review describes recent insights into the role of PPARγ in the macrophage lineage, and its potential function in the regulation of inflammatory responses and atherosclerosis. J. Leukoc. Biol. 66: 733–739; 1999.
Lung surfactant proteins (SP-A and SP-D) in non-adaptive host responses to infection
Authors: Holmskov Uffe 
Published: January 2018

Abstract
The lung surfactant proteins A and D (SP-A and SP-D) are collectins composed of C-type lectin domains attached to collagen regions. SP-A and SP-D are mainly found in the surfactant covering the pulmonary epithelial cells, but are also produced by cells lining the gastrointestinal tract. The main role of SP-A and SP-D is to interact directly with carbohydrate on the surface of microbial pathogens, thereby initiating a variety of effector mechanisms. This review focuses on the non-adaptive host responses of SP-A and SP-D to infection. Interaction of SP-A and SP-D with phagocytes is discussed and the structure and function of the putative receptors for SP-A and SP-D is presented. SP-A and SP-D seem to be regulated in a way similar to acute-phase proteins in the course of inflammation and evidence for the involvement of SP-A and SP-D as immunomodulators as well as their role in clearing allergens and modulating effector mechanisms in allergic reactions is discussed. J. Leukoc. Biol. 66: 747–752; 1999.
Heat shock response: presence and effects in burn patient neutrophils
Authors: Rodeberg David A , Meyer Joseph G , Babcock George F 
Published: January 2018

Abstract
Heat shock proteins (HSPs) are present in neutrophils (PMNs) from critically ill patients. We investigated whether HSPs were present in PMNs from burn patients and whether heat shock contributed to the functional defects observed in burn PMNs. Using both flow cytometry and Western blot techniques it was observed that inducible HSP72 (iHSP72) was present in PMNs and leukocytes from burn patients, especially in patients with inhalation injury. Similar to burn PMNs, and in contrast to normal cells, heat shocked PMNs (43° incubation) expressed iHSP72 and were unable to increase the expression of CD11b/CD18 in response to pro-inflammatory stimuli. Degranulation after pro-inflammatory stimuli was decreased for both burn- and heat-shocked PMNs when compared to normal controls. In burn PMNs these functional abnormalities were mainly due to decreased quantities of proteins (CD11b, albumin, B12 binding protein, β-glucuronidase) present within cytoplasmic granules. However, in heat-shocked PMNs the abnormalities were primarily related to abnormal exocytosis. In conclusion, our data show that decreased quantities of cytoplasmic granule proteins and, to a smaller degree, defective exocytosis are involved in the functional abnormalities observed in burn PMNs. J. Leukoc. Biol. 66: 773–780; 1999.
Respective involvement of TGF-β and IL-4 in the development of Langerhans cells and non-Langerhans dendritic cells from CD34+ progenitors
Authors: Caux Christophe , Massacrier Catherine , Dubois Bertrand , Valladeau Jenny , Dezutter-Dambuyant Colette , Durand Isabelle , Schmitt Daniel , Saeland Sem 
Published: January 2018

Abstract
In vivo, dendritic cells (DC) form a network comprising different populations. In particular, Langerhans cells (LC) appear as a unique population of cells dependent on transforming growth factor β (TGF-β) for its development. In this study, we show that endogenous TGF-β is required for the development of both LC and non-LC DC from CD34+ hematopoietic progenitor cells (HPC) through induction of DC progenitor proliferation and of CD1a+ and CD14+ DC precursor differentiation. We further demonstrate that addition of exogenous TGF-β polarized the differentiation of CD34+ HPC toward LC through induction of differentiation of CD14+ DC precursors into E-cadherin+, Lag+CD68−, and Factor XIIIa−LC, displaying typical Birbeck granules. LC generated from CD34+ HPC in the presence of exogenous TGF-β displayed overlapping functions with CD1a+ precursor-derived DC. In particular, unlike CD14+-derived DC obtained in the absence of TGF-β, they neither secreted interleukin-10 (IL-10) on CD40 triggering nor stimulated the differentiation of CD40-activated naive B cells. Finally, IL-4, when combined with granulocyte-macrophage colony-stimulating factor (GM-CSF), induced TGF-β-independent development of non-LC DC from CD34+ HPC. Similarly, the development of DC from monocytes with GM-CSF and IL-4 was TGF-β independent. Collectively these results show that TGF-β polarized CD34+ HPC differentiation toward LC, whereas IL-4 induced non-LC DC development independently of TGF-β. J. Leukoc. Biol. 66: 781–791; 1999.
Regulation of CD163 on human macrophages: cross-linking of CD163 induces signaling and activation
Authors: van den Heuvel Michel M , Tensen Cornelis P , van As Jaco H , van den Berg Timo K , Fluitsma Donna M , Dijkstra Christine D , Döpp Ed A , Droste Anne , van Gaalen Floris A , Sorg Clemens , Högger Petra , Beelen Rob H J 
Published: January 2018

Abstract
CD163 is a member of the group B scavenger receptor cysteine-rich (SRCR) superfamily. This study describes aspects of the tissue distribution, the regulation of expression, and signal transduction after cross-linking of this receptor at the cell surface of macrophages. CD163 showed an exclusive expression on resident macrophages (e.g., red pulp macrophages, alveolar macrophages). The expression was inducible on monocyte-derived macrophages by glucocorticoids but not by interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interferon-γ. The combination of IL-4 or GM-CSF with glucocorticoids resulted in a further increase. Subcellular analysis of alveolar macrophages by immunoelectron microscopy showed a plasma membrane localization of the antigen. Cross-linking of CD163 with monoclonal antibody induced a protein tyrosine kinase-dependent signal that resulted in (1) slow-type calcium mobilization, (2) inositol triphosphate production, and (3) secretion of IL-6 and GM-CSF. The data suggest a function for the SRCR-superfamily receptor CD163 in the regulation of inflammatory processes by macrophages. J. Leukoc. Biol. 66: 858–866; 1999.
Tyrosine kinase-regulated small GTPase translocation and the activation of phospholipase D in HL60 granulocytes
Authors: Houle Martin G , Naccache Paul H , Bourgoin Sylvain 
Published: January 2018

Abstract
We focus on the mechanisms of regulation of phospholipase D (PLD) activity. Three agonists known to stimulate PLD activity, fMet-Leu-Phe (fMLP), phorbol 12-myristate 13-acetate (PMA) and V4+-OOH, induced a differential translocation of ADP-ribosylation factor (ARF), RhoA, and protein kinase Cα (PKCα), all cofactors for PLD activation. Whereas fMLP recruited all three proteins to membranes, V4+-OOH only elicited RhoA translocation and PMA induced ARF and PKCα translocation. Three tyrosine kinases inhibitors, ST-638, methyl 2,5-dihydroxycinnamate, and genistein reduced fMLP-stimulated PLD activity by up to 80%. Furthermore, tyrosine kinase inhibitors reduced the fMLP-induced increase of GTPγS-stimulated PLD activity in membranes and recruitment of ARF, RhoA, and PKCα to the membrane fraction. The data suggest that a tyrosine phosphorylation event is located upstream of the translocation of ARF, RhoA, and PKCα in the signaling pathway leading to PLD activation by fMLP. RO 31-8220, a specific inhibitor of PKC, reduced PMA-induced PLD activity by 80% in intact HL60 granulocytes but enhanced fMLP-stimulated PLD activity by 60%. Although PMA alone had no effect on RhoA recruitment to the membrane fraction, in the presence of RO 31-8220 the levels of membrane-bound RhoA were increased. The levels of membrane-bound ARF and PKCα were unaffected by RO 31-8220 during PMA stimulation. In contrast, fMLP-induced recruitment of ARF and RhoA was insensitive to RO 31-8220 but PKCα translocation was increased. We propose that RhoA translocation may be regulated by PKC in an ATP-independent manner. Furthermore, increased fMLP-induced PKCα translocation in the presence of RO 31-8220 may partially account for the synergistic activation of PLD observed when both fMLP and RO 31-8220 are used together in intact HL60 cells. J. Leukoc. Biol. 66: 1021–1030; 1999.
High-level expression of IkB-b in the surface epithelium of the colon: in vitro evidence for an immunomodulatory role
Authors: Wu Gary D , Huang Ning , Wen Xiaoming , Keilbaugh Sue A , Yang Hongyun 
Published: January 2018

Abstract
The intestinal epithelium is spatially segregated into two compartments, one containing undifferentiated cells in a proliferative state and one with non-proliferative differentiated cells. Although this epithelium can produce many immune-modulating substances, emerging evidence suggests that the differentiated cell compartment is less immune responsive. Indeed, it is the differentiated cellular compartment that represents the interface between the highly antigenic luminal environment and the mucosal immune system. The NF-κB/rel family of transcriptional activators play a critical role in regulating the inflammatory response by activating a wide variety of immune-modulating genes. These transcription factors are maintained in an inactive state in the cytoplasmic compartment by interaction with inhibitory proteins of the IκB family. In this study we show by immunohistochemistry that IκB-β is expressed at high levels specifically in the differentiated surface epithelium of the colonic mucosa. Using a naturally occurring compound found in the colon of vertebrates, butyrate, we provide evidence in an intestinal cell line that alteration of IκB-β expression can modulate the transcriptional activation of the interleukin-8 (IL-8) gene by preventing the nuclear translocation of NF-κB proteins. Therefore, the expression of IκB-β in the differentiated surface epithelium of the colon may help these cells act as an immunological barrier to prevent activation of the mucosal immune system. J. Leukoc. Biol. 66: 1049–1056; 1999.