bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of alpha L beta 2 integrin avidity in transendothelial chemotaxis of mononuclear cells.
Authors: Weber C , Lu C F , Casasnovas J M , Springer T A 
Published: December 2022

Abstract
The leukocyte integrin alpha L beta 2 (LFA-1) is important in transendothelial migration. Since it is not fully understood how LFA-1 mediates transmigration, we studied the effects of alpha L and beta 2 cytoplasmic domain mutants that alter LFA-1 adhesiveness for intercellular adhesion molecule-1. Monocyte chemotactic protein-1 (MCP-1) induced LFA-1-dependent transendothelial migration of Jurkat and J-beta 2.7 transfectants coexpressing the MCP-1 receptor CCR2B and wild-type alpha L. No transendothelial chemotaxis was observed with truncation mutants of the alpha L cytoplasmic tail, which rendered LFA-1 constitutively active or locked LFA-1 in a low avidity state unresponsive to cellular activation. Moreover, transendothelial chemotaxis of lymphoblastoid SLA transfectants was abolished by truncation of the beta 2 cytoplasmic domain, but not by mutation of its TTT motif, which is important in phorbol ester-induced adhesion. These data indicate that transmigration may require both alpha L and beta 2 cytoplasmic domains. We further show that MCP-1-induced transendothelial chemotaxis of PBMC was inhibited by sustained activation of LFA-1 with Mn2+ or a stimulatory mAb to beta 2. Dimeric soluble intercellular adhesion molecule-1 also reduced transendothelial chemotaxis of PBMC. Taken together, our data suggest that transendothelial chemotaxis of mononuclear cells may involve dynamic changes in LFA-1 avidity.
In vivo inhibition of nuclear factor-kappa B activation prevents inducible nitric oxide synthase expression and systemic hypotension in a rat model of septic shock.
Authors: Liu S F , Ye X , Malik A B 
Published: December 2022

Abstract
We determined the in vivo function of LPS-induced nuclear factor-kappa B (NF-kappa B) activation in mediating inducible nitric oxide synthase (iNOS) mRNA and protein expression, and systemic arterial hypotension in a rat model of septic shock. LPS (8 mg/kg i.v.) challenge of rats activated NF-kappa B within 15 min in lung tissue, and the response persisted up to 4 h. NF-kappa B activation preceded the induction of iNOS mRNA. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kappa B effective in cellular studies, prevented NF-kappa B activation in vivo and reduced iNOS mRNA expression and the increase in iNOS activity activated by LPS. At PDTC concentrations of 50, 100, and 200 mg/kg, the reductions of iNOS mRNA were 20, 46, and 48%, and the reductions in iNOS activity were 59, 66, and 75%, respectively. The PDTC concentration-dependent reductions in iNOS activity produced similar decreases in plasma nitrite/nitrate concentrations. PDTC also prevented the decrease in arterial blood pressure induced by LPS. These results demonstrate that activation of NF-kappa B is a critical in vivo regulatory mechanism mediating LPS-induced iNOS expression and the resultant systemic hypotension.
Role of passenger leukocytes in allograft rejection: effect of depletion of donor alveolar macrophages on the local production of TNF-alpha, T helper 1/T helper 2 cytokines, IgG subclasses, and pathology in a rat model of lung transplantation.
Authors: Sekine Y , Bowen L K , Heidler K M , Van Rooijen N , Brown J W , Cummings O W , Wilkes D S 
Published: December 2022

Abstract
Acute lung allograft rejection is believed to be initiated by passenger leukocytes, such as alveolar macrophages (AM), in the donor organ, which release TNF-alpha, and present alloantigens to host lymphocytes, to up-regulated Th1 cellular and humoral immunity. However, the role of donor AM in local TNF-alpha synthesis, and their ability to induce local Th1 cellular and humoral immunity have not been evaluated. By depleting Brown Norway (BN, RT1n) rat lung allografts of AM before transplantation into Lewis rat (LEW, RT1(1)) recipients, the current study determined the role of donor AM in including the production of TNF-alpha, IFN-gamma (Th1 cytokine), IL-4 (Th2 cytokine), IgG subtypes, and rejection pathology in the allograft. The data show that compared with untreated BN allografts, pretransplant depletion of donor lung AM resulted in significantly less TNF-alpha, and IFN-gamma production in allograft bronchoalveolar lavage fluid with variable effects on local IL-4 production. Depletion of AM in the donor lung before transplantation affected the local production of several IgG subclasses. However, pretransplant depletion of donor AM had no effect on the development of the pathology of severe acute rejection. These data show that donor AM have a central role in the local synthesis of TNF-alpha and induce the production of IFN-gamma and IgG subtypes, locally, during acute lung allograft rejection. However, depletion of AM before transplantation does not prevent the development of severe acute rejection in BN rat lungs, transplanted into LEW recipients.
Dual role of IL-12 in early and late stages of murine collagen type II arthritis.
Authors: Joosten L A , Lubberts E , Helsen M M , van den Berg W B 
Published: December 2022

Abstract
IL-12 can promote Th1 responses, and early administration of IL-12 during immunization was shown to enhance expression of autoimmune collagen-induced arthritis (CIA). We now studied the impact of IL-12 at the stage of disease expression and during established CIA in DBA-1 mice. Accelerated onset and enhanced severity were provoked when i.p. injections of 100 ng of murine IL-12 (mIL-12) were given around the time of arthritis onset. Moreover, the onset of CIA could be ameliorated with anti-mIL-12 Abs, indicating that IL-12 is a pivotal mediator in the expression of CIA. In addition, the effect of anti-mIL-12 treatment was analyzed in established CIA. Continued treatment did not suppress established arthritis. Instead, these mice showed an impressive exacerbation of arthritis shortly after cessation of anti-mIL-12 treatment, indicative of impairment of endogenous control. Exaggerated disease was characterized by massive granulocyte influx and enhanced expression of IL-1 beta and TNF-alpha mRNA in the synovial tissue. Subsequently, we treated established collagen arthritis with recombinant mIL-12 for 7 days. Profound suppression of the arthritis score was noted, including reduced influx of cells and diminished cartilage damage. Tenfold enhanced levels of IL-10 were detected in sera of mIL-12-treated mice, and up-regulated mRNA levels of IL-10, IFN-gamma, and IL-12 were measured in synovial tissue. Finally, the anti-inflammatory effect of IL-12 on CIA could be reversed by coadministration of anti-IL-10 Abs. This study indicates that IL-12 has a stimulatory role in early arthritis expression, whereas it has a suppressive role in the established phase of collagen arthritis.
Up-regulation of Fas and the costimulatory molecules B7-1 and B7-2 on peripheral lymphocytes in autoimmune B6/gld mice.
Authors: Weintraub J P , Eisenberg R A , Cohen P L 
Published: December 2022

Abstract
C57BL/6-gld/gld (B6/gld) mice have a point mutation in the gene for Fas ligand (FasL) resulting in nonfunctional FasL protein. We hypothesized that the lack of normal Fas/FasL interactions in these mice might result in abnormalities of Fas expression. Thus, we compared spleen cells from B6/gld mice and normal B6 control mice. While B6 spleen cells consisted of two main populations, Fashigh (high Fas expression) and Faslow (low Fas expression), nearly all B6/gld spleen cells were Fashigh. Two-color immunofluorescence revealed that the Fashigh and Faslow populations in the B6 spleen were Thy-1.2+ (T cells) and IgM+ (B cells), respectively, whereas both T cells and B cells in the B6/gld spleen were Fashigh, indicating that Fas expression is increased on B cells in the B6/gld spleen. This phenomenon was age related and restricted to peripheral lymphocytes. In addition to Fas, B6/gld splenic B cells showed increased expression of the costimulatory molecule B7-2, while the related costimulatory molecule B7-1 was up-regulated on both B cells and T cells in the B6/gld spleen. In vitro, both B cells and T cells from the B6/gld spleen showed an increase in susceptibility to apoptosis mediated by soluble anti-Fas Ab. These results suggest that some lymphocytes in B6/gld mice are primed to undergo Fas-mediated apoptosis, but are unable to do so due to the absence of functional FasL. Further study of such abnormal lymphocytes in the B6/gld spleen may elucidate the nature of autoimmunity in these mice.
Venoms of North American Snakes and Their Relationship
Authors: Githens Thomas S. , Butz Lewis W. 
Published: December 2022

Summary and Conclusions
The venoms of six species of North American rattlesnakes, which were studied, contain identical or almost identical toxic principles. The toxic principles of the copperhead and moccasin are identical or almost so, but differ to some extent from those of the rattlesnakes. The venom of Crotalus terrificus the dog-faced rattlesnake of Central and South America, and the venom of Bothrops atrox, the fer de lance, contain principles differing entirely from those of the Nearctic rattlesnakes as regards their antigenic properties. Rattlesnake venoms contain, in addition to their acutely toxic principles, other components, which have the power to bind antibodies, but which are not acutely toxic to the pigeons.
Immunization and the Nitrogenenous Constituents of the Blood
Authors: Guyer M. F. , Lepkovsky S. 
Published: December 2022

Abstract
In connection with teh studies of the senior author (Guyer,1918, 1920, 1924), on the possibilities of modifying the germ plasm through serological reaction, it speedily became evident that if one is not to work wholly in the dark more must be known of the chemical changes which occur in the blood incident to the building of antibodies against foreign proteins or against the products of injury to an animal's own tissues (Guyer, 1923,1926).
In a study on the amino-nitrogen of the blood of rabbits, made in this laboratory, Mabel G. Boyden, research assistant of the senior author, found that in 48 rabbits the average content of amino-nitrogen for normal whole rabbit blood was 10.814 mgm.per 100cc.
Heterophile Antibodies in Serum Sickness
Authors: Davidsohn I. 
Published: December 2022

Summary
The sera of 21 patients afflicted with horse serum sickness, whose blood was obtained during or at various intervals following the disease, were examined for agglutinins and hemolysins for sheep blood. Every one of them contained agglutinins for sheep blood, in titers varying from 1:4 to 1:64. Of 450 cases with no history of serum sickness, only 19 or 4.2 per cent showed agglutinins for sheep blood. All these 19 positive cases agglutinated only in the lowest dilution used (1:4). Four of the 21 cases showed a very remarkable increase of antisheep hemolysin, complete hemolysis occurring in dilutions: (1:192) (= 0.0026 cc.), (1:384) (= 0.0013 cc.), (1:768) (= 0.0006 cc.), (1:1536) (= 0.00032 cc.), while the highest titer found normally in a large series of control cases was 1:128 (= 0.004 cc.). Very fresh sheep erythrocytes were somewhat less agglutinable than older ones; their hemolysis was not influenced by age. Only one serum lost its antisheep agglutinins on standing. An immediate reaction in one patient (case 2) following injection of horse serum is brought in connection with the finding of agglutinins in a blood specimen obtained 20 hours following injection. The agglutinins were probably present before the injection of serum. In one of the serum sickness cases (no. 9) and one of the control cases (no. 13) the development of agglutinins following the injection of horse serum was observed by repeated titrations. Two cases (nos. 13 and 22) developed agglutinins following injection of horse serum, but no serum sickness. Three cases (nos. 10, 11 and 19) showed no agglutinins and no serum sickness following injection, while 6 cases found free from agglutinins before injection of serum did not develop serum sickness. A case of bovine serum sickness did not develop antisheep hemolysins. The heterophile nature of the agglutinins and hemolysins found in the serum of patients with horse serum sickness was established by absorption experiments.
Ricinoleated Vaccines
Authors: Kozlowski Anthony 
Published: December 2022

Abstract
In his recent explanation of the phenomenon of ulceration caused by the injection of sodium-ricinoleate solution into animals, Larson (1) suggested that it is due to the use of barium in the preparation of ricinoleic acid because it is practically impossible to remove traces of barium. As regards the author's recent work (2), however, Larson is not justified in attributing the ulcerative action of the vaccine to that cause. The method of purification of ricinoleic acid which was used and which will appear shortly in the Journal of Bacteriology, insures a preparation of the fatty acid free from barium. Moreover, even if there had been traces of barium in the ricinoleic-acid preparation, which had not been removed by sulfuric acid and repeated extraction of the fatty acid with ether, the minute amounts of that element not detectable by the usual chemical methods would not have been sufficient to cause any irritation of the animal tissues when injected with a 1-per-cent solution of sodium ricinoleate.
Dual Role of Dendritic Cells in the Induction and Down-Regulation of Antigen-Specific Cutaneous Inflammation
Authors: Krasteva Maya , Kehren Jeanne , Horand Françoise , Akiba Hitoshi , Choquet Geneviève , Ducluzeau Marie-Thérèse , Tédone Rosine , Garrigue Jean-Luc , Kaiserlian Dominique , Nicolas Jean-François 
Published: December 2022

AbstractWe have previously reported that contact sensitivity (CS) to dinitrofluorobenzene (DNFB) in C57BL/6 mice was mediated by MHC class I-restricted CD8+ T cells and down-regulated by MHC class II-restricted CD4+ T cells. In this study, we analyzed the contribution of dendritic cells (DC) in the induction of these two T cell subsets endowed with opposite functions. Hapten-pulsed skin- and bone marrow-derived DC, obtained from either normal C57BL/6 mice or from MHC class II (I+II−) and MHC class I (I−II+)-deficient mice, were tested for their ability to prime normal mice for CS to dinitrofluorobenzene. Expression of MHC class I molecules by transferred DC was mandatory both for the induction of CS and for the generation of hapten-specific CD8+ T cells in lymphoid organs. I+II− DC were as potent as I+II+ DC in priming for CS, demonstrating that activation of effector CD8+ T cells can occur independently of CD4+ T cell help. I−II+ DC could not immunize for CS, although they could sensitize for a delayed-type hypersensitivity reaction to protein Ags. Moreover, I−II+ DC injected simultaneously with cutaneous sensitization down-regulated the inflammatory response, suggesting that hapten presentation by MHC class II molecules could prime regulatory CD4+ T cells. These results indicate that DC can present haptenated peptides by both MHC class I and class II molecules and activate Ag-specific CD8+ effector and CD4+ regulatory T cell subsets, concurrently and independently.
CpG DNA Rescue from Anti-IgM-Induced WEHI-231 B Lymphoma Apoptosis via Modulation of IκBα and IκBβ and Sustained Activation of Nuclear Factor-κB/c-Rel
Authors: Yi Ae-Kyung , Krieg Arthur M. 
Published: December 2022

AbstractUnmethylated CpG dinucleotides in particular base contexts in oligonucleotides (CpG DNA) rescue WEHI-231 cells from anti-IgM-induced cell cycle arrest and apoptosis. Anti-IgM rapidly elevated the levels of NFκB p50/c-Rel heterodimers followed by a decline of p50/c-Rel heterodimers by 3 h and a concomitant increase of p50/p50 homodimers. In contrast, CpG DNA induced and maintained the levels of p50/c-Rel heterodimers in the presence or absence of anti-IgM, while control non-CpG DNA failed to induce NFκB activation. Anti-IgM induced IκBα degradation followed by increased IκBα protein levels. The levels of IκBβ were increased after anti-IgM treatment. In contrast, CpG DNA, but not non-CpG DNA, induced sustained IκBα and IκBβ degradation in the presence or absence of anti-IgM. Inhibition of IκB degradation blocked CpG DNA-induced NFκB activation and expression of c-myc. Prevention of NFκB activation by inhibiting IκB degradation also suppressed the ability of CpG DNA to rescue WEHI-231 cells from anti-IgM-induced apoptosis. These results indicate that CpG DNA-mediated sustained activation of NFκB depends on the degradation of IκBα and IκBβ and is required for the CpG DNA-mediated anti-apoptosis gene expression and the protection against anti-IgM-induced apoptosis of WEHI-231 cells.
Decreased Resistance of TNF Receptor p55- and p75-Deficient Mice to Chronic Toxoplasmosis Despite Normal Activation of Inducible Nitric Oxide Synthase In Vivo
Authors: Yap George S. , Scharton-Kersten Tanya , Charest Hugues , Sher Alan 
Published: December 2022

AbstractThe importance of TNF-α in host defense to the intracellular parasite, Toxoplasma gondii, was investigated in mice lacking both the p55 and p75 receptors for this cytokine. Upon i.p. infection with the avirulent ME49 strain, knockout mice were capable of limiting acute i.p. infection, but succumbed within 3 to 4 wk to a fulminant necrotizing encephalitis. Receptor-deficient mice harbored higher cyst burdens and exhibited uncontrolled tachyzoite replication in the brain. The lack of TNF receptors did not adversely affect the development of a type 1 IFN-γ response. In vitro studies with peritoneal macrophages stimulated with IFN-γ and tachyzoites indicated that under limiting concentrations of IFN-γ, nitric oxide-mediated toxoplasmastatic activity is TNF-α dependent. However, this requirement is overcome by increasing the dose of IFN-γ. Furthermore, both ex vivo and in vivo studies demonstrated that inducible nitric oxide synthase induction in the peritoneal cavity and brain is unimpaired in receptor-deficient mice. Thus, TNF-dependent immune control of T. gondii expansion in the brain involves an effector function distinct from inducible nitric oxide synthase activation.
Activation of Complement by Mannose-Binding Lectin on Isogenic Mutants of Neisseria meningitidis Serogroup B
Authors: Jack Dominic L. , Dodds Alister W. , Anwar Natasha , Ison Catherine A. , Law Alex , Frosch Matthias , Turner Malcolm W. , Klein Nigel J. 
Published: December 2022

Abstract
Mannose-binding lectin (MBL) is a serum protein that has been demonstrated to activate the classical complement pathway and to function directly as an opsonin. Although MBL deficiency is associated with a common opsonic defect and a predisposition to infection, the role of the protein in bacterial infection remains unclear. We have investigated MBL binding to Neisseria meningitidis serogroup B1940 and three isogenic mutants, and the subsequent activation of the two major isoforms of C4 (C4A and C4B) by an associated serine protease, MASP. The mutants lacked expression of the capsular polysaccharide (siaD−), the lipo-oligosaccharide (LOS) outer core that prevented LOS sialylation (cpsD−), or both capsule and LOS outer core (cps−). Using flow cytometry, it was possible to detect strong MBL binding to the cps− and cpsD− mutants over a wide range of concentrations. In contrast, minimal or no MBL binding was detected on the parent organism, with binding to siaD− only at higher MBL concentrations. C4 was activated and bound by mutants that had previously bound MBL/MASP, but there was no significant difference in the amounts of C4A and C4B bound. When sialic acid residues were removed from the parent organism by neuraminidase treatment, the binding of both MBL and C4 increased significantly. Our results suggest that MBL may bind to and activate complement on these encapsulated organisms, and the major determinants of these effects are the LOS structure and sialylation.
Differences in Nitric Oxide Production by Superficial and Deep Human Articular Chondrocytes: Implications for Proteoglycan Turnover in Inflammatory Joint Diseases
Authors: Häuselmann H. J. , Stefanovic-Racic M. , Michel B. A. , Evans C. H. 
Published: December 2022

Abstract
During inflammatory joint diseases, chondrocytes are exposed to cytokines such as IL-1 that induce the synthesis of nitric oxide (NO). Chondrocytes from different zones of the articular cartilage are known to have different metabolic properties. In the present study, we have demonstrated that chondrocytes recovered from the superficial zone of normal, human, articular cartilage synthesize approximately 2 to 3 times as much NO in response to IL-1 as chondrocytes recovered from the deep zone of the same cartilage. Production of NO by normal cartilage in response to IL-1 was also found to decrease with age. Addition of the NO synthase inhibitor NG-monomethyl-l-arginine (l-NMA, 1 mM) blocked NO production by cells of both zones. l-NMA completely reversed the suppression of proteoglycan synthesis imposed by IL-1 in deep chondrocytes, but produced only partial reversal in superficial cells. As noted previously, IL-1 failed to elicit a strong catabolic response in cultures of human cartilage. In the presence of l-NMA, however, IL-1 reduced the metabolic t1/2 of proteoglycans by approximately 50% in both the superficial and deep zones. This suggests that NO has, directly or indirectly, an anticatabolic effect in human cartilage. These data confirm the metabolic heterogeneity of human chondrocytes, and suggest that NO may be involved to different degrees as an endogenous modulator of the turnover of the cartilaginous matrix in different zones of articular cartilage.
Streptococcal Cell Wall-Induced Arthritis: Requirements for IL-4, IL-10, IFN-γ, and Monocyte Chemoattractant Protein-1
Authors: Schimmer Ralph C. , Schrier Denis J. , Flory Craig M. , Laemont Keith D. , Tung David , Metz Alan L. , Friedl Hans P. , Conroy Mary Carol , Warren Jeffrey S. , Beck Beatrice , Ward Peter A. 
Published: December 2022

AbstractIntra-articular injection of streptococcal cell wall Ag followed by i.v. challenge (“reactivation”) results in a destructive lymphocyte-dependent monoarticular arthritis. To further define the role of immune mechanisms in the model, Abs to Th1 and Th2-related cytokines were evaluated. Treatment of rats with antibodies to IL-4 reduced swelling, while treatment with anti-IL-10 or anti-IFN-γ either had no effect or slightly enhanced the inflammatory response. These results suggest that Th-2 immune mechanisms may be, at least in part, operative in the model. To more precisely define the role of IL-4, the effects of anti-IL-4 on monocyte chemoattractant protein-1 (MCP-1) expression were evaluated. Initial studies demonstrated that mRNA (as determined by in situ hybridization) and protein (as determined by immunofluorescence) for MCP-1 were detectable in inflamed synovial tissue in a time-dependent manner. Anti-IL-4 treatment significantly reduced the expression of mRNA for MCP-1 24 and 72 h after reactivation. In addition, anti-MCP-1 inhibited swelling and reduced influx of 111In-labeled T cells. These data suggest that the reactivation model of streptococcal cell wall Ag-induced arthritis is Th-2 dependent, and that an inter-relationship exists between IL-4 and the expression of MCP-1.