bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombin induces IL-6 production in fibroblasts and epithelial cells. Evidence for the involvement of the seven-transmembrane domain (STD) receptor for alpha-thrombin.
Authors: Sower L E , Froelich C J , Carney D H , Fenton J W , Klimpel G R 
Published: January 2023

Abstract
alpha-Thrombin is a multifunctional serine protease that has an important role in the coagulation cascade, wound healing, and inflammatory response. In this study, we show that thrombin induces IL-6 production in human epithelial cells and fibroblasts. ELISA and Northern blot analyses showed that physiologic concentrations of thrombin (0.1-1 micrograms/ml) induced IL-6 production in human lung fibroblasts, skin fibroblasts, and epithelial cells. Hirudin, a thrombin inhibitor, completely blocked IL-6 induction by thrombin. Treatment of fibroblasts with inactivated diisopropylphosphofluoridate (DIP)-alpha-thrombin, gamma-thrombin, or trypsin had no effect on IL-6 production. In contrast, treatment with the thrombin-tethered ligand receptor peptide TRP-7 (SFLLRNP) induced IL-6 production, but at lower levels than that induced by native alpha-thrombin. Finally, IL-6 pretreatment of lung or skin fibroblasts resulted in the enhanced production of IL-6 following exposure to thrombin. These results suggest that fibroblasts and epithelial cells may represent a significant source of IL-6 in the inflammatory response to tissue injury, and that cytokine production is an important biologic consequence of thrombin's interaction with its seven-transmembrane domain (STD) receptor.
Antigen presentation by epithelial cells induces anergic immunoregulatory CD45RO+ T cells and deletion of CD45RA+ T cells.
Authors: Marelli-Berg F M , Weetman A , Frasca L , Deacock S J , Imami N , Lombardi G , Lechler R I 
Published: January 2023

Abstract
The immunoregulatory effects of alloantigen presentation by tissue parenchymal cells to resting peripheral blood CD4+ T cells was investigated. Coculture of CD45RO+ (memory) and CD45RA+ (naive) T lymphocytes with primary cultures of MHC class II-expressing epithelial cells rendered both populations of T cells hyporesponsive to a subsequent challenge by the same MHC molecule expressed on EBV-transformed lymphoblastoid B cell lines. However, the mechanisms responsible for the allospecific hyporesponsiveness were distinct. For the CD45RO+ T cells, responsiveness was restored by subsequent culture in the presence of IL-2; the addition of IL-2 had no effect on the reactivity of the CD45RA+ T cells. In contrast, the naive T cells were protected from the induction of nonresponsiveness by the presence of a neutralizing anti-CD95 Ab during the culture with thyroid follicular cells. In addition, the hyporesponsive CD45RO+ T cells effected linked suppression, in that they inhibited proliferation against a third-party DR alloantigen when the third-party alloantigen was coexpressed with the DR Ag against which hyporesponsiveness had been induced. These results suggest that recognition of Ag by T cells on tissue parenchymal cells plays an important role in the maintenance of peripheral T cell tolerance, inducing nonresponsiveness in naive and memory T cells by distinct mechanisms.
Depressed Langerhans cell migration and reduced contact hypersensitivity response in mice lacking TNF receptor p75.
Authors: Wang B , Fujisawa H , Zhuang L , Kondo S , Shivji G M , Kim C S , Mak T W , Sauder D N 
Published: January 2023

Abstract
Epidermal Langerhans cells (LC) belong to the dendritic cell family and represent the major APC within the skin. LC capture epicutaneous Ag, migrate into regional lymph nodes, and present Ag to T cells, thereby initiating primary immune response. The migratory properties of LC are an essential component of their function. The molecular mechanisms responsible for LC migration are far less defined. However, evidence has been accumulating to suggest that TNF-alpha, a major proinflammatory cytokine, plays an important role in promoting DC migration. To confirm the role of TNF-alpha in LC migration and to examine which type of TNF receptor signaling is involved in such an event, we utilized gene-targeted knockout mice lacking TNF receptor p55 or p75. The migration of LC was assessed by examining the frequency of hapten-bearing cells in draining lymph nodes following hapten FITC painting, and the accumulation of dendritic cells in draining lymph nodes after intradermal injection of TNF-alpha. While LC migration was normal in p55-deficient mice, the migration was markedly depressed in p75-deficient mice. Receptor p75-deficient mice also demonstrated a hyporesponsiveness in allergen-induced contact dermatitis, but a normal responsiveness in irritant-induced contact dermatitis. These results suggest that p75-dependent signaling plays a crucial role in the migration of LC and in the initiation of cutaneous immune responses.
Potent induction of a neutrophil and eosinophil-rich infiltrate in vivo by human mast cell tryptase: selective enhancement of eosinophil recruitment by histamine.
Authors: He S , Peng Q , Walls A F 
Published: January 2023

Abstract
Tryptase is the most abundant protein constituent of the secretory granules of human mast cells, but little is known of the contribution of this serine proteinase in acute allergic reactions. We have purified tryptase from human lung tissue by immunoaffinity procedures, and have investigated its potential to provoke an inflammatory infiltrate in vivo. Within 6 h of injection into the skin of guinea pigs, the accumulation of large numbers of neutrophils and eosinophils was observed, and those eosinophils closest to the injection site were partially degranulated. Similarly, injection of tryptase into the peritoneum of mice, even in quantities as low as 5 ng, stimulated the ingress of neutrophils. The response was dose dependent at 3, 6, and 16 h, with increases in median numbers of up to 400-fold. At the later time points eosinophil numbers were increased by up to 10-fold, and there were elevations also in the numbers of lymphocytes and macrophages. In both models, the actions of tryptase appeared to be dependent on an intact catalytic site. Coinjection of heparin with tryptase had relatively little effect on tryptase-induced responses. On the other hand, although histamine did not itself stimulate cell accumulation, over a range of concentrations it altered the cellular composition of the infiltrate induced by tryptase. Addition of histamine to tryptase provoked selective increases in eosinophil numbers of up to fivefold in the mouse peritoneum. Tryptase may provide an important stimulus for granulocyte recruitment in allergic disease.
TNF and lymphotoxin-alpha polymorphisms associated with common variable immunodeficiency: role in the pathogenesis of granulomatous disease.
Authors: Mullighan C G , Fanning G C , Chapel H M , Welsh K I 
Published: January 2023

Abstract
A subgroup of common variable immunodeficiency (CVID) patients have distinct clinical features, particularly granulomata splenomegaly, characteristic blood lymphocyte phenotype, and elevated circulating TNF levels. To investigate the genetic basis for this phenotype, 150 CVID patients and 200 controls were genotyped for six biallelic TNF and lymphotoxin-alpha (LT alpha) polymorphisms and eight class I and II HLA loci using PCR and sequence specific primers (PCR-SSP) sequence-specific primers. Clinical and immunophenotypic data were collected for 90 patients to examine associations with CVID patient subgroups. The presence of granulomata (22% of patients) was strongly associated with splenomegaly, T and B lymphopenia, reduced CD4+ CD45RA+ T cells, and CD8+ CD57+ lymphocytosis, confirming the concept of a subgroup of patients with distinct clinical and laboratory features. The uncommon TNF +488A allele was strongly associated with this subgroup (p = 0.0005). The association between "granulomatous" CVID and TNF +488A was independent of HLA class I and II associations. We postulate that the presence of the TNF +488A allele, or alleles in linkage disequilibrium with it, contributes to the high levels of TNF and granulomatous complications characteristic of this subgroup of patients.
Yersinia invasin, a bacterial beta1-integrin ligand, is a potent inducer of lymphocyte motility and migration to collagen type IV and fibronectin.
Authors: Arencibia I , Suárez N C , Wolf-Watz H , Sundqvist K G 
Published: January 2023

Abstract
The Yersinia pseudotuberculosis invasin protein was found to be a potent inducer of pseudopodia formation and chemotactic and haptotactic migration in human T lymphocytes. Checkerboard analysis confirmed that migration was directional. The Yersinia invasin triggered migration of otherwise poorly migratory normal T cells on fibronectin and in particular on collagen type IV, and augmented the migration of leukemic T cell lines on these components. Invasin-induced lymphocyte migration was inhibited by staurosporin that selectively prevented pseudopodia formation but, noteworthy, augmented adhesion. The motogenic and attractant properties of invasin (Inv) were mediated via beta1-integrins, as shown by lack of effect of Inv on the motility of a beta1-integrin-negative lymphoid cell line and inhibition of invasin-induced lymphocyte motility by anti-beta1 Abs. Inv was markedly more effective than the extracellular matrix components fibronectin, collagen type IV, and laminin, which also interact with lymphocyte beta1-integrins, with respect to induction of pseudopodia, chemotaxis, and haptotaxis. Thus, Yersinia invasin is a model ligand for induction of lymphocyte motility via beta1-integrins. The extraordinary capacity of Inv to trigger and guide T lymphocyte motility and potentiate lymphocyte migration to extracellular matrix components may be of pathogenetic significance for the movement of lymphocytes to extraintestinal sites secondary to Yersinia infection.
Biologic activity of proteoglycan macrophage colony-stimulating factor.
Authors: Suzu S , Kimura F , Ota J , Motoyoshi K , Itoh T , Mishima Y , Yamada M , Shimamura S 
Published: January 2023

Abstract
We compared the biologic activities of 85-kDa macrophage-CSF (85-kDa M-CSF), which is fully active, and a proteoglycan M-CSF (PG-M-CSF). Both originate from the same precursor, but the latter retains the carboxyl-terminal portion, which must be proteolytically removed from the precursor to generate 85-kDa M-CSF and which is uniquely modified by a chondroitin sulfate glycosaminoglycan chain. PG-M-CSF supported the formation of murine macrophage colonies such as 85-kDa M-CSF. Furthermore, PG-M-CSF stimulated the proliferation of murine bone marrow macrophages, an M-CSF-dependent murine cell line, and an M-CSF-responsive human cell line established by transfer of the human M-CSF receptor gene. PG-M-CSF and 85-kDa M-CSF had equivalent specific biologic activities on a molar basis in all bioassays. The activity of PG-M-CSF was not affected by enzymatically removing the glycosaminoglycan chain when assayed by the formation of macrophage colonies and proliferation of the bone marrow macrophages. We analyzed the phosphorylation on tyrosine residue(s) of the M-CSF receptor in response to these M-CSFs that trigger mitogenic responses. PG-M-CSF rapidly (within 10 min) induced receptor phosphorylation in human cells with the same potency as 85-kDa M-CSF. These results indicate that PG-M-CSF is not a latent form or precursor of 85-kDa M-CSF but a fully biologically active cytokine.
Receptor expression and responsiveness of human dendritic cells to a defined set of CC and CXC chemokines.
Authors: Sozzani S , Luini W , Borsatti A , Polentarutti N , Zhou D , Piemonti L , D'Amico G , Power C A , Wells T N , Gobbi M , Allavena P , Mantovani A 
Published: January 2023

Abstract
Dendritic cells (DC) are migratory cells that exhibit complex trafficking properties in vivo. The present study was designed to characterize receptor expression and responsiveness to chemoattractants of human DC obtained from PBMC by culture with granulocyte/macrophage-CSF and IL-13. DC expressed appreciable levels of the CCR1, CCR2, and CCR5 receptors for the CC chemokines and the chemokine receptors CXCR1, CXCR2, and CXCR4. DC increased intracellular free calcium and migrated in response to the CC chemokines MCP-3, MCP-4, RANTES, MIP-1alpha, MIP-1beta, and MIP-5/HCC2 and the CXC chemokine SDF-1. In contrast, the CC chemokines MCP-1 and eotaxin had little or no activity in the concentration range tested (up to 1 microg/ml). IL-8 and Gro-beta (CXC) and lymphotactin (C chemokines) were also inactive. DC did not respond to 5-HETE, whereas platelet-activating factor was an active agonist. Selected chemokines active on DC in terms of migration and calcium fluxes were examined for their capacity to modulate endocytosis and Ag presentation. Under conditions in which TNF-alpha was active, MCP-1, MCP-3, MIP-1alpha, and RANTES did not affect these two responses. Thus, among hemopoietic elements, DC respond to a unique set of CC and CXC chemokines, and their responsiveness is restricted to migration with no effect on Ag capture and presentation. Chemokines may play a role in the trafficking of DC under resting or stimulated conditions. Chemokine receptors expressed in DC are likely to underlie HIV infection of this cell type.
Observations on the Proposed Gold Chloride Titration for Determining the Toxicity of Diphtheria Toxin
Authors: Sanderson Everett S. , Yoe John H. 
Published: January 2023

Summary and Conclusions
The results of the foregoing experiments may be summarized as follows: Six different diphtheria toxins when tested by the “gold chloride” and guinea pig methods failed to show any parallelism as to toxicity.The green color zone produced in mixtures of gold chloride and toxic broths is not specific for toxin: Inactivated (heated) and non-inactivated toxins gave almost identical gold chloride titration figures.The amount of gold chloride necessary to bring about the maximum green coloration with toxic broths can be entirely altered by changing the initial hydrogen ion concentration and the buffer capacity of the broths.Several batches of uninoculated 1 per cent dextrose extract broth gave a green color zone when mixed with gold chloride.Maximum green color in mixtures of broths and gold chloride is obtained at an approximate pH of 4.5.The gold chloride test does not appear to be a satisfactory method for standardizing bacterial toxins in its present form.
Microglia Are More Efficient Than Astrocytes in Antigen Processing and in Th1 But Not Th2 Cell Activation
Authors: Aloisi Francesca , Ria Francesco , Penna Giuseppe , Adorini Luciano 
Published: January 2023

AbstractMicroglia and astrocytes, two glial cell populations of the central nervous system, present Ag and stimulate T cell proliferation, but it is unclear whether they preferentially activate Th1 or Th2 responses. We have investigated the efficiency of microglia and astrocytes in the presentation of OVA peptide 323-339 or native OVA to Th1 and Th2 cell lines from DO11.10 TCR transgenic mice. Upon stimulation with IFN-γ, microglia express MHC class II molecules, CD40, and ICAM-1 and efficiently present OVA 323-339, leading to T cell proliferation and production of IL-2 and IFN-γ by Th1 and of IL-4 by Th2 cells. IFN-γ-treated astrocytes, which express MHC class II and ICAM-1, present OVA 323-339 less efficiently to Th1 cells but are as efficient as microglia in inducing IL-4 secretion by Th2 cells. However, astrocytes are much less potent than microglia in presenting naturally processed OVA peptide to either T cell subset, indicating inefficient Ag processing. The capacity of astrocytes and microglia to stimulate Th1 and Th2 cells depends on their MHC class II expression and does not involve ICAM-1, B7-1, or B7-2 molecules. However, CD40-CD40L interactions contribute to Th1 activation by microglia. These data suggest that microglia may play a role in the activation of Th1 and Th2 cells, whereas astrocytes would restimulate mainly Th2 responses in the presence of appropriate peptides. This differential capacity of brain APC to restimulate Th1 and Th2 responses may contribute to the reactivation and regulation of local inflammatory processes during infectious and autoimmune diseases.
Kinetics of Establishing the Memory B Cell Population as Revealed by CD38 Expression
Authors: Ridderstad Anna , Tarlinton David M. 
Published: January 2023

AbstractIn this report, we detail changes in the expression of CD38 on murine B cells during the course of a T cell-dependent immune response. CD38 is expressed on all naive B cells but is down-regulated on isotype-switched B cells from both the germinal centers (GCs) and the foci of Ab-forming cells which arise during the first weeks of the response. The down-regulation on GC B cells, however, is reversible since Ag-specific IgG1 B cells with high levels of CD38 are apparent by 2 wk postimmunization. These cells have characteristics that resemble recirculating memory B cells, in that they are small and bind low levels of peanut agglutinin. Such characteristics indicate that the restoration of CD38 levels is coincidental with the transition from GC to memory B cell. Using this observation, we plotted the development of the memory population and the demise of the GC reaction as a function of time after immunization. Our results indicate that the GC reaction ceases gradually over many weeks rather than suddenly, which corresponds with the formation of the memory B cell population. Furthermore, by segregating memory B cells and GC B cells, it was possible to assess the in vitro survival characteristics of each compared with naive B cells. These experiments demonstrated that memory B cell survival in vitro was comparable with naive B cell survival but less than the survival seen for bcl-2-transgenic B cells, whereas GC B cell survival, as expected, was very poor. Hence, by resolving murine Ag-specific memory B cells and GC B cells, we have been able to quantify the development of the memory B cell population.
Differential Activation of T Cells by Natural Antigen Peptide Analogues: Influence on Autoimmune and Alloimmune In Vivo T Cell Responses
Authors: Soares Luis R. B. , Orr Patricia L. , Garovoy Marvin R. , Benichou Gilles 
Published: January 2023

Abstract
Recent studies using synthetic altered peptide ligands (Analogues) have led to the fine dissection of TCR-mediated T cell functions elicited by Ag recognition. Certain Analogues behave as full agonists of the antigenic peptide while others are partial agonists in that they only trigger selected T cell functions. Additionally, peptide Analogues can behave as antagonists by inhibiting functions of T cell clones when coincubated with the wild-type peptide. In fetal thymic organ cultures, synthetic altered peptide ligands can impact T cell repertoire selection. However, the influence of naturally occurring peptide Analogues on T cell immunity in vivo remains hypothetical. We previously reported that, in B10.A mice, immunogenicity and tolerogenicity of the self-MHC class I peptide, Ld 61-80, were influenced by the presentation of a cross-reactive self-peptide, Kk 61-80. Here, we show that Kk 61-80 self-peptide represents a partial agonist of Ld 61-80 in that it induced the proliferation but not the lymphokine production of Ld 61-80-primed T cells. Next, we showed that presentation of Kk 61-80 Analogue peptide mediated T cell tolerance toward Ld 61-80 self-peptide. Alternatively, when Ld protein represented an alloantigen displayed on transplanted cells, immunization with Kk 61-80 Analogue sensitized recipient mice to Ld 61-80 peptide, thus inducing potent immune responses to donor cells. These results show that the presentation of natural Analogue peptides may represent an essential component of T cell responses involved in autoimmunity and transplant rejection.
The Structure of Avian CD5 Implies a Conserved Function
Authors: Koskinen Riitta , Göbel Thomas W. F. , Tregaskes Clive A. , Young John R. , Vainio Olli 
Published: January 2023

Abstract
The chicken CD5 cDNA was isolated by COS cell expression cloning utilizing a novel mAb 2-191. The cDNA contains a 1422-nucleotide open reading frame encoding a mature protein with 32% and 30% identity to mouse and human CD5 polypeptides, respectively. The molecule consists of a 330-amino acid extracellular region with three repeats of the scavenger receptor cysteine-rich domain, a 29-amino acid hydrophobic transmembrane domain, and a 93-amino acid cytoplasmic tail. The cytoplasmic region contains motifs that are highly conserved between species, including several potential phosphorylation sites. The chicken CD5 is a 64-kDa phosphorylated glycoprotein with a protein core of 57 kDa as determined by immunoprecipitation and SDS-PAGE analysis. αβ T cells express a homogeneously high level of CD5, whereas low or intermediate CD5 expression on γδ T cells depends on their tissue location. In contrast to human and mouse, CD5 is found at low levels on all chicken B cells. The high conservation of structural features, as well as signaling motifs, implies a conserved role for CD5 both in lymphocyte development and function.
Phosphatidylinositol 3′-Kinase and SH2-Containing Inositol Phosphatase (SHIP) Are Recruited by Distinct Positive and Negative Growth-Regulatory Domains in the Granulocyte Colony-Stimulating Factor Receptor
Authors: Hunter Melissa G. , Avalos Belinda R. 
Published: January 2023

Abstract
Activation of both positive and “negative” or anti-proliferative signals has emerged as a common paradigm for regulation of cell growth through cell surface receptors that regulate immune responses. SHP-1 and -2 and the novel 5′-inositol phosphatase SHIP have recently been shown to function as growth inhibitory molecules in immune receptor signaling. In the current study, we have identified distinct regions in the granulocyte colony-stimulating factor receptor (G-CSFR) distal to the conserved box 2 motif necessary for mitogenesis, which exert positive and negative influences on growth signaling in Ba/F3 pro-B lymphoid cells. The region spanning amino acids 682 to 715 mediates activation of phosphatidylinositol 3′(PI3)-kinase. Activation of PI3-kinase leads to inhibition of apoptosis, promotion of cell survival, and enhanced proliferative responses to G-CSF. We show that the region of 98 amino acids in the distal tail of the class I G-CSFR down-modulates proliferative signaling, not only in myeloid cell lines, as previously reported, but also in Ba/F3 cells. This same region recruits SHIP to the signaling cascade through a mechanism involving Shc, with the formation of Shc/SHIP complexes. Our data suggest a model in which PI3-kinase and SHIP coordinately regulate growth signaling through the G-CSFR.