bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil inhibitory factor prevents neutrophil-dependent lung injury.
Authors: Barnard J W , Biro M G , Lo S K , Ohno S , Carozza M A , Moyle M , Soule H R , Malik A B 
Published: December 2022

Abstract
Neutrophil inhibitory factor (NIF) is a recently cloned 41-kDa protein from the canine hookworm that binds CD11b/CD18 and inhibits CD11b/CD18-dependent neutrophil adhesion. We evaluated NIF's effects on neutrophil-dependent lung injury in guinea pigs. Pulmonary vascular endothelial CD54 (ICAM-1) was induced in buffer-perfused lungs by 90-min exposure to 1000 U/ml TNF-alpha. Human neutrophils (2 x 10(7)) were added to the perfusate and activated by 5 x 10(-9) PMA; in some lungs, the neutrophils were pretreated with NIF (100 nM) before their addition to the perfusate. Lung injury was assessed by wet:dry weight ratio, and neutrophil uptake by lung myeloperoxidase (MPO) activity. HUVEC exposed to TNF-alpha for 90 min were assayed for neutrophil adhesion, and we compared PMA-stimulated neutrophil adhesion to endothelial cells and fibrinogen-coated plates. PMA-induced pulmonary edema (lung wet:dry ratio increased from 8.8 +/- 0.7 to 18.8 +/- 4.4) was inhibited by NIF (10.0 +/- 1.0). Lung MPO activity concomitantly decreased from 17.1 +/- 6.1 to 8.7 +/- 1.8 U/mg dry lung tissue in the NIF-treated group, similar to controls (6.9 +/- 2.0). Endothelial monolayer experiments confirmed that NIF reduced neutrophil adherence (basal adhesion of 11 +/- 3% increased to 30 +/- 5% with TNF-alpha pretreatment of endothelial cells, an increase that was reduced to 10 +/- 4% with NIF). Moreover, NIF prevented PMA-induced neutrophil adhesion to fibrinogen, a CD11b/CD18-dependent event, but produced a smaller decrease in adherence to endothelial cells, which also involves CD11a/CD18 integrins. These studies indicate that NIF prevents neutrophil-dependent lung vascular injury by inhibiting neutrophil adhesion to the TNF-alpha-activated endothelium.
Stimulation of CD40 with purified soluble gp39 induces proinflammatory responses in human monocytes.
Authors: Kiener P A , Moran-Davis P , Rankin B M , Wahl A F , Aruffo A , Hollenbaugh D 
Published: December 2022

Abstract
CD40 is a glycoprotein of about 50 kDa that plays a crucial role in B cell growth and differentiation. It is found on the surface of B cells, follicular dendritic cells, monocytes, and some endothelial, epithelial, and carcinoma cells. Engagement of CD40 with anti-CD40 mAbs, gp39 expressed on the cell surface or soluble forms of gp39, primes B cells to efficiently respond to subsequent stimulatory signals leading to B cell proliferation, differentiation, and isotype switching. Peripheral monocytes also express CD40 on the cell surface and expression in increased following treatment with IFN-gamma. Using a soluble murine CD8/human gp39 fusion protein (sgp39) we have found that CD40 plays a crucial role in the regulation of monocyte function. Stimulation of human peripheral monocytes with sgp39 induced homotypic aggregation and significantly increased the expression of several cell-surface proteins including CD54, MHC class II, CD86, and CD40. Soluble gp39 also dramatically enhanced monocyte survival, preventing the onset of apoptosis that normally occurs upon withdrawal of serum. Finally, in the absence of any costimulatory molecules, sgp39 stimulated monocytes to produce TNF-alpha, IL-1 beta, IL-6, and IL-8. These results suggest that ligation of CD40 on human monocytes induces phenotypic changes that would be expected to influence T cell activation by the monocyte and also to enhance or prolong inflammatory responses.
TGF-beta enhances macrophage ability to produce IL-10 in normal and tumor-bearing mice.
Authors: Maeda H , Kuwahara H , Ichimura Y , Ohtsuki M , Kurakata S , Shiraishi A 
Published: December 2022

Abstract
In the present study, we demonstrate that TGF-beta is capable of enhancing macrophage ability to produce IL-10 in normal and EL4 tumor-bearing mice. We found the increase in IL-10 in ascitic fluid and IL-10 mRNA expression in macrophages in parallel with the TGF-beta level and tumor progression. The macrophage production of IL-10 in the tumor-bearing mice was significantly enhanced without LPS stimulation in vitro, compared with normal controls. To clarify the mechanism wherein increased IL-10 production was induced, anti-TGF-beta or anti-IL-10 Abs were administered to EL4-bearing mice. Administration of anti-TGF-beta Ab led to a reduction in the IL-10 contents in ascitic fluid of tumor-bearing mice; however, anti-IL-10 Ab administration did not prevent the increase in TGF-beta contents. Enhanced IL-10 production and mRNA expression of macrophages from the tumor-bearing mice were also reduced by anti-TGF-beta Ab administration. Both anti-TGF-beta and anti-IL-10 Ab administration restored the TNF-alpha production by macrophages in EL4-bearing mice. In normal macrophages, in vitro pretreatment with TGF-beta 1 potentiated IL-10 production, and when natural TGF-beta 1 was administered to normal mice, the recovered peritoneal macrophages showed enhanced IL-10 production. Based on the above findings it can be concluded that TGF-beta enhances macrophage ability to produce IL-10, which sheds a new light on the role of TGF-beta in the immune system.
Classical complement pathway activation on nucleated cells. Role of factor H in the control of deposited C3b.
Authors: Ollert M W , David K , Bredehorst R , Vogel C W 
Published: December 2022

Abstract
The restriction of alternative complement pathway activation in fluid phase or on nonactivator surfaces has been described as the major physiologic function of the complement regulatory protein factor H. In this study, we provide evidence that factor H is also a restriction factor of classical pathway activation on the surface of nucleated cells. We found that C3b was rapidly converted to inactivated C3b (iC3b) on human SK-MEL-93-2 melanoma cells after classical pathway activation with the murine monoclonal IgG3 Ab R24 directed against the disialoganglioside surface Ag GD3. The SK-MEL-93-2 cells are nonactivators of the alternative pathway and express neither CR1 (CD35) nor the C3b-cleaving protease p65. The cells are further characterized by the expression of only moderate amounts of DAF (CD55) and approximately 5 x 10(3) MCP (CD46) molecules/cell. FACS analysis and direct quantitation using [125I]factor H revealed high level binding of factor H to the melanoma cells (5.6 x 10(6) molecules/cell) during classical pathway activation. The binding of factor H could be inhibited under conditions that inactivate the classical complement pathway (EGTA and heat treatment), but not by factor B depletion of the serum, demonstrating that classical pathway activation was responsible for factor H binding. Treatment of factor B-depleted serum with neutralizing concentrations of polyclonal anti-factor H resulted in the prolonged presence of intact C3b on the cells and a significantly reduced generation of iC3b. The increased amount of C3b on these cells correlated with a 2.65-fold greater rate of cell death. In contrast, the increase in cell death effected by neutralizing concentrations of anti-CD46 or anti-CD55 Ab was only 0.13- or 0.35-fold, respectively. In addition, the supplementation of serum with purified factor H decreased the extent of lysis of the cells. Collectively, these data provide experimental evidence that factor H, through its cofactor activity for C3b degradation, is involved in the restriction of the classical pathway of complement on the surface of nucleated cells, a function that to date has been exclusively attributed to the membrane regulatory proteins CD35 and CD46.
An important role for the chemokine macrophage inflammatory protein-1 alpha in the pathogenesis of the T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis.
Authors: Karpus W J , Lukacs N W , McRae B L , Strieter R M , Kunkel S L , Miller S D 
Published: December 2022

Abstract
Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-mediated, inflammatory demyelinating disease of the central nervous system (CNS) that serves as a model for the human demyelinating disease, multiple sclerosis. A critical event in the pathogenesis of EAE is the entry of both Ag-specific T lymphocytes and Ag-nonspecific mononuclear cells into the CNS. In the present report we investigated the role of two C-C chemokines (macrophage inflammatory protein-1 alpha (MIP-1 alpha) and monocyte chemotactic protein-1) and a C-x-C chemokine (MIP-2) in the pathogenesis of EAE. Production in the CNS of MIP-1 alpha, but not that of MIP-2, a rodent homologue of IL-8, or monocyte chemotactic protein-1, correlated with development of severe clinical disease. Administration of anti-MIP-1 alpha, but not that of anti-monocyte chemotactic protein-1, prevented the development of both acute and relapsing paralytic disease as well as infiltration of mononuclear cells into the CNS initiated by the transfer of neuroantigen peptide-activated T cells. Ab therapy could also be used to ameliorate the severity of ongoing clinical disease. Anti-MIP-1 alpha did not affect the activation of encepahlitogenic T cells as measured by cytokine secretion, surface marker expression, and ability to adoptively transfer EAE. These results demonstrate that MIP-1 alpha plays an important role in directing the chemoattraction of mononuclear inflammatory cells in the T cell-mediated autoimmune disease, EAE.
Effects of recombinant dimeric TNF receptor on human inflammatory responses following intravenous endotoxin administration.
Authors: Suffredini A F , Reda D , Banks S M , Tropea M , Agosti J M , Miller R 
Published: December 2022

Abstract
Effects of dimeric TNF receptor (p80) Fc (TNFR:Fc) on acute phase responses were evaluated in 18 volunteers given endotoxin (4 ng/kg i.v.). Subjects were randomized to receive either placebo (n = 6), low dose TNFR:Fc (10 mg/m2 i.v., n = 6), or high dose TNFR:Fc (60 mg/m2 i.v., n = 6). TNFR:Fc blocked plasma TNF bioactivity (p = 0.001) and increased, in a dose-ordered fashion, TNF immunoactivity (p &lt; 0.001). TNFR:Fc decreased secondary cytokine levels including IL-1 beta (p = 0.007), IL-8 (p &lt; 0.001), IL-1 receptor antagonist (p &lt; 0.001), granulocyte-CSF (p = 0.03), and growth regulated peptide-alpha (p = 0.001) but not macrophage inflammatory protein-1 alpha or IL-10. Low dose, but not high dose, TNFR:Fc blunted or delayed the release of epinephrine and cortisol (p &lt; or = 0.026). Despite the absence of plasma TNF bioactivity, high dose TNFR:Fc was less immunosuppressive than low dose TNFR:Fc as measured by cytokine and stress hormone responses. Endotoxin-related symptoms were not altered by TNFR:Fc and the febrile response was delayed but not diminished (p = 0.004). Increases in cardiac index (72 +/- 19%) and heart rate (60 +/- 10%) and decreases in systemic vascular resistance index (47 +/- 7%) were unaltered by TNFR:Fc. These data suggest that the inflammatory response to endotoxin can escape from high levels of circulating TNF-blocking activity and redundant pathways, independent of circulating TNF, can sustain inflammation and clinical responses caused by acute endotoxemia.
Oligoclonal expansion of CTLs directed against a restricted number of dominant minor histocompatibility antigens in hemopoietic chimeras.
Authors: Brochu S , Baron C , Hétu F , Roy D C , Perreault C 
Published: December 2022

Abstract
To understand how T cells respond to allogeneic minor histocompatibility Ags (MiHAs), we studied the fate of Thy-1.1+ lymphocytes, as well as their TCR usage and functional activity, in irradiated LP (Thy-1.2+) recipients transplanted with a mixture of C57BL/6 (Thy-1.2+) hemopoietic progenitors supplemented with either low or high numbers of B6.PL lymphocytes (Thy-1.1+). Mice transplanted with low numbers of T cells experienced a dramatic expansion (&gt; or = 10(5)-fold) of donor Thy-1.1+/CD8+ cells during the first 15 days post-transplant. Flow-cytometric analysis and sequencing of junctional nucleotide sequences showed that the nature of this expansion was oligoclonal and involved primarily one or a few clones using V beta 5.1 or V beta 8.1 TCR elements. Expanded T lymphocyte populations displayed MHC-restricted cytotoxicity for a restricted number of MiHAs, that were found in only two peaks following fractionation of LP MiHAs by reverse-phase HPLC. Expansion of donor T cells was limited to the spleen, and short-lived in these recipients that became healthy long-term chimeras without any signs of graft-vs-host disease (GVHD). In contrast, mice transplanted with high numbers of T cells (GVHD+) showed proliferation of Thy-1.1+ donor cells not only in the spleen, but also in the thymus, and recipients died rapidly of GVHD. These results show that: 1) in the MiHA-incompatible transplantation setting, lack of GVHD cannot be explained simply by the absence of antihost T cell responses, 2) GVHD+ recipients present a massive thymic infiltration by donor mature T lymphocytes, and 3) antihost T cell responses are oligoclonal in nature and targeted to only a few MiHAs. These findings shed new light on the pathogenetic mechanisms involved in GVHD and on the selection of the T cell repertoire involved in response to immunodominant MiHAs.
Triggering of a sustained calcium response through a p56lck-dependent pathway by exogenous ganglioside GM1 in human T lymphocytes.
Authors: Gouy H , Debré P , Bismuth G 
Published: December 2022

Abstract
Various biologic effects induced by free external gangliosides, including cell-signaling events, have been described in several cell systems. We show in this report that free monosialoganglioside GM1, following its rapid and saturable binding to the cell membrane of human Jurkat T cells, triggers in a few seconds a sustained elevation of the intracellular free calcium concentration. It also induces in parallel the early tyrosine phosphorylation of numerous proteins, including phospholipase C gamma-1. Parallel experiments performed with asialo-GM1 or the ceramide part of the molecule do not reproduce these effects, demonstrating the prominent role played by the sialylated part of the ganglioside. A marked conversion of the T cell-specific tyrosine kinase p56lck to a slow migrating 60-kDa form is also found following GM1 addition. It is accompanied in the same time by an increased kinase activity in p56lck immunoprecipitates. Finally, the marked calcium response and tyrosine phosphorylations triggered by GM1 cannot be observed in a p56lck-negative T cell variant. Together these results demonstrate that the monosialoganglioside GM1 can behave as an authentic activation molecule on human T lymphocytes, likely through a p56lck tyrosine kinase-dependent pathway.
Cross-linking of CD45 on NK cells stimulates p56lck-mediated tyrosine phosphorylation and IFN-gamma production.
Authors: Xu X , Chong A S 
Published: December 2022

Abstract
The cross-linking of low-affinity Fc gamma RIIIA on NK cells with specific mAbs or aggregated IgG stimulates both cytotoxic activity and cytokine production. In addition, the interaction of NK cells with certain tumor cells can also stimulate cytokine production and cytotoxic activity. The identity of the molecules on the tumor cell or NK cells involved in this stimulation currently has not been defined. We have reported previously that cross-linking of CD45 and the CD45RO isoform on IL-2-activated NK cells or the NK cell line NK3.3 results in the stimulation of IFN-gamma production. We report here that this effect is specific, because cross-linking of CD45 does not stimulate the expression of cytotoxic activity. Consistent with studies suggesting that cross-linking of CD45 results in reduced phosphatase activity, inhibition of tyrosine phosphatase activity by pharmacologic means also resulted in enhanced tyrosine kinase activity and, ultimately, increased IFN-gamma production. Biochemical analyses and immunofluorescence studies suggest that the tyrosine kinase associated with CD45 is p56lck and that cross-linking of CD45 results in the activation of p56lck. Thus, CD45 may regulate p56lck kinase, which initiates the cascade of intracellular tyrosine phosphorylation events that lead to IFN-gamma transcription and secretion in NK 3.3 cells.
Multiple lineages of tumors express a common tumor antigen, P1A, but they are not cross-protected.
Authors: Ramarathinam L , Sarma S , Maric M , Zhao M , Yang G , Chen L , Liu Y 
Published: December 2022

Abstract
Whether tumors of different lineages share common Ags is a critical issue for understanding anti-tumor immune responses and for designing Ag-specific tumor immunotherapy. Because of lack of cross-protection among individually derived tumors, it has been proposed that tumor Ags are specific for individual tumors. Here we show that lack of cross-protection is not due to lack of a shared tumor Ag. Thus, a plasmocytoma J558 transfected with the costimulatory molecule B7 activates a cross-reactive CTL response in vivo. The major Ag recognized by the cross-reactive CTL is P1A, which is expressed in mastocytoma P815, plasmocytoma J558, and fibrosarcoma Meth A. Surprisingly, no significant cross-protection can be detected among P1A-expressing tumors after immunization with either P1A-expressing or B7-transfected P815 cells. Our results demonstrate that multiple lineages of tumors are not cross-protected even though they share a tumor Ag that can be recognized by CTL. These results have important implications for tumor immunotherapy.
Pulmonary surfactant protein A mediates enhanced phagocytosis of Mycobacterium tuberculosis by a direct interaction with human macrophages.
Authors: Gaynor C D , McCormack F X , Voelker D R , McGowan S E , Schlesinger L S 
Published: December 2022

Abstract
During initial infection with Mycobacterium tuberculosis, bacteria that reach the distal airspaces of the lung are phagocytosed by alveolar macrophages in the presence of pulmonary surfactant. Here we have examined the role of surfactant-associated protein A (SP-A) in phagocytosis of the virulent Erdman strain of M. tuberculosis by human monocyte-derived macrophages (MDMs) and human alveolar macrophages (HAMs). Macrophage monolayers incubated with soluble SP-A from alveolar proteinosis patients (APP SP-A4) and recombinant rat SP-A (SP-Ahyp) demonstrated enhanced adherence of M. tuberculosis, 82 +/- 17% and 49 +/- 18%, respectively. Removal of SP-A from monolayers by washing before adding bacteria did not diminish the enhanced adherence. Fluorescence microscopy demonstrated that washed monolayers contained intracellular rather than surface-bound SP-A. These studies indicated a direct interaction between SP-A and the macrophage in mediating enhanced adherence of M. tuberculosis. Consistent with this interpretation, macrophage monolayers formed on human or rat SP-A (substrate SP-A) demonstrated enhanced adherence of M. tuberculosis to their apical surface (APP SP-A and native rat SP-A increased M. tuberculosis adherence by 102 +/- 16% and 102 +/- 25%, respectively). Electron microscopy demonstrated increased numbers of phagocytosed bacteria in APP SP-A-treated MDM cross-sections. SP-A proteins devoid of carbohydrate failed to enhance M. tuberculosis adherence to macrophages. In contrast, heat-denatured APP SP-A enhanced adherence of bacteria equivalent to that of intact glycoprotein. Thus, the carbohydrate moieties of SP-A appear to be critical in the SP-A-macrophage interaction. Finally, mannan and anti-mannose receptor Ab completely inhibited the enhanced phagocytosis of M. tuberculosis observed with APP SP-A, providing evidence for up-regulation of macrophage mannose receptor activity. These studies implicate SP-A as an important modulator of alveolar macrophage function that results in an enhanced potential for M. tuberculosis to gain access to its intracellular niche.
Chemically detoxified lipid A precursor derivatives antagonize the TNF-alpha-inducing action of LPS in both murine macrophages and a human macrophage cell line.
Authors: Tanamoto K 
Published: December 2022

Abstract
The chemically synthesized disaccharide precursor of lipid A (406) has been demonstrated to reduce its activity in mice by an order of 10(5) or more by replacing the hydroxyl groups with succinyl or acetyl residues. In the present study, these chemically detoxified synthetic lipid A precursors were found to antagonize the LPS action of inducing TNF-alpha in both murine peritoneal macrophages and in human monocyte-macrophage cell line THP-1. These preparations were found to antagonize the induction of TNF-alpha in murine macrophages by both stimulants of LPS and untreated 406, which acts as an agonist in the murine system, in a dose-dependent manner. Complete inhibition by succinylated 406 occurred at 10-fold excesses of the antagonist. Succinylated precursor also antagonized the TNF-alpha-inducing action of LPS in human cell line THP-1. The precursor itself also exhibited antagonism in this assay. The activity of the succinylated 406, however, was much more potent than that of the unmodified precursor. These derivatives do not inhibit either the Limulus gelation activity of LPS, or the induction of TNF-alpha in macrophages by zymosan, indicating that the inhibition is not caused by molecular interaction and that the inhibition is specific to LPS action. These findings suggest common features in murine macrophage and human monocytic cell receptors. They also suggest the importance of the substituents on the hydroxyl groups of 3-hydroxy fatty acids of the nonreducing glucosamine of lipid A for the activity and for transformation to the antagonistic structure.
Endogenous IL-10 protects mice from death during septic peritonitis.
Authors: van der Poll T , Marchant A , Buurman W A , Berman L , Keogh C V , Lazarus D D , Nguyen L , Goldman M , Moldawer L L , Lowry S F 
Published: December 2022

Abstract
IL-10 production during endotoxic shock is part of a protective mechanism that involves IL-10-induced inhibition of TNF synthesis. We sought to determine the role of IL-10 in septic peritonitis induced by cecal ligation and puncture (CLP). CLP led to a rapid induction of IL-10 mRNA in various organs of C57BI/6 mice. In liver, IL-10 mRNA was detectable within 1 h following CLP, while in spleen and lungs, IL-10 mRNA was detected from 2 to 4 h and onward. IL-10 protein became detectable in plasma 2 h after CLP, reaching peak concentrations after 12 h (12.7 +/- 5.7 ng/ml). Pretreatment (-2 h) with anti-IL-10 mAb resulted in higher plasma TNF levels following CLP when compared with mice treated with control mAb. Plasma IL-1 activity and IFN-gamma remained undetectable in virtually all mice. Anti-IL-10 enhanced mortality after CLP (p &lt; 0.05 by log-rank test). Addition of anti-TNF mAb did not influence the increased mortality associated with anti-IL-10 treatment. Septic peritonitis is associated with sustained production of IL-10 in various organs, which serves to protect the host against lethality.