bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antigenic challenge of immunized mice induces endogeneous production of IL-3 that increases histamine synthesis in hematopoietic organs.
Authors: Lebel B , Schneider E , Piquet-Pellorce C , Machavoine F , Kindler V , Luffau G , Dy M 
Published: December 2022

Abstract
Antigenic challenge of Nippostrongylus brasiliensis-infected mice induces a striking increase in histidine decarboxylase (HDC) activity in both spleen and bone marrow cells. This enhancement takes place within 1 h after injection, with a maximum at 4 h and a return to pretreatment values 20 h later. It is associated with the appearance of IL-3 in the sera of these mice. In addition, the intracellular histamine content in both hematopoietic organs is concomitantly increased. A similar injection of worm Ag into normal mice has no significant effect. Comparable enhancement of HDC activity and intracellular histamine content with almost identical kinetics is promoted by i.v. injection of rIL-3 into normal mice. Moreover, HDC levels in infected mice are increased to the same extent in response to either specific antigen or rIL-3 injection. Taken together these results support the conclusion that antigenic challenge of immunized mice induces endogeneous IL-3 which, in turn, promotes a rapid increase in histamine synthesis in hematopoietic organs.
IL-1 binds to high affinity receptors on human osteosarcoma cells and potentiates prostaglandin E2 stimulation of cAMP production.
Authors: Rodan S B , Wesolowski G , Chin J , Limjuco G A , Schmidt J A , Rodan G A 
Published: December 2022

Abstract
IL-1 is a potent bone resorbing agent. Its mechanism of action is unknown, but the presence of osteoblasts was shown to be necessary for IL-1 stimulation of bone resorption by isolated osteoclasts. This study examines the presence of IL-1R and IL-1 effects in osteoblastic cells from a clonal human osteosarcoma cell line, Saos-2/B-10. We found that the binding affinity and the number of binding sites increases substantially during the postconfluent stage. Scatchard and curve-fitting analysis revealed one class of high affinity binding sites, with Kd/Ki's of 40 +/- 17 pM (mean +/- SD) for IL-1 alpha (n = 5) and 9 +/- 7 pM for IL-1 beta (n = 5) and 2916 +/- 2438 (n = 6) receptors/cell. Incubation of the cells with 125I-IL-1 alpha (100 pM) at 4 degrees C, followed by incubation at 37 degrees C up to 4 h, revealed internalization of receptor-bound IL-1 alpha. Chemical cross-linking studies showed that the IL-1R in Saos-2/B-10 cells had a molecular mass of approximately 80 kDa. To assess the biologic effect of IL-1 in Saos-2/B-10 cells, we determined PGE2 content and adenylate cyclase activity. Although IL-1 had no effect on PGE2 synthesis, both IL-1 alpha and IL-1 beta enhanced PGE2 stimulation of adenylate cyclase two- to four-fold in a dose-dependent manner. The half-maximal effect for IL-1 alpha was seen at 8 to 10 pM and for IL-1 beta at 0.6 to 1.8 pM. IL-1 did not enhance basal adenylate cyclase or stimulation by parathyroid hormone, isoproterenol, or forskolin. IL-1 enhancement of PGE2-stimulated adenylate cyclase was detected between 1 to 2 h, was maximal at 4 to 5 h, was not prevented by cycloheximide treatment, and was seen in membranes from IL-1 pretreated cells. These data show effects of IL-1 on a human osteoblast-like cell line that are mediated by high affinity receptors. These IL-1 effects could contribute to the biologic action of IL-1 on bone.
Regulation of granulomatous inflammation in murine schistosomiasis. IV. Antigen-induced suppressor T cells down-regulate proliferation and IL-2 production.
Authors: Fidel P L , Boros D L 
Published: December 2022

Abstract
In murine schistosomiasis mansoni the cell-mediated immune response to the deposited eggs is mediated by CD4+ delayed-type hypersensitivity effector T (TDH) cells that produce vigorous granulomatous responses in the liver and intestines of acutely infected animals. The response is significantly down-modulated in chronically infected mice by Ag-specific Ts cells. The present study was undertaken to establish an in vitro model by which TDH-Ts cell interactions could be analyzed. To this end, Ts cells were induced in vitro by preculture of chronic or acute infection spleen cells with soluble egg Ag (SEA) for 48 h. The induced cells suppressed the SEA-specific proliferation of acute infection spleen cells by 80 to 95%. The induced suppressor cells were Ag specific in both induction and elicitation of function, and were not cytotoxic to the acute infection splenic target cells. Suppression by the induced cells was manifested within the first 24 h of the SEA-induced response as IL-2 produced by acute infection spleen cells was suppressed 62%. Phenotypic analysis by flow cytometry of the induced suppressor cells showed that CD8+ cells from acute infection spleens and CD4+ and CD8+ cells from chronic infection spleens were effector Ts cells. Taken together, CD4+ and CD8+ SEA-specific Ts cells can be induced in vitro to effectively suppress the SEA-specific lymphoproliferation and IL-2 production of acute infection spleen cells. Establishment of this in vitro model will allow us to further analyze the mechanisms of Ts cell-mediated suppression of TDH cells.
Growth factor-initiated proliferation of mouse embryonic fibroblasts induces cytotoxicity by natural killer cells and by a non-cytolysin cytotoxin in natural killer granules.
Authors: Khalil N , Battistuzzi S C , Kraut R P , Schwarz L C , Greenberg A H 
Published: December 2022

Abstract
NK cells preferentially kill normal embryonic fibroblasts. Because embryonic cells are growth factor responsive and maintain high proliferative rates, we examined the requirement for growth factor-initiated proliferation for NK susceptibility. Murine embryonic fibroblasts made quiescent in defined medium lacking growth factors were relatively resistant to NK cytolysis. However, reinitiation of proliferation with basic fibroblast growth factor (bFGF) or epidermal growth factor enhanced lysis in a dose-dependent fashion. TGF-beta, which blocked cell division, did not enhance cytotoxicity. Additionally, growth inhibition by prolonged incubation at confluence suppressed lysis. The enhanced NK cytotoxicity of bFGF-stimulated fibroblasts was caused by a post-binding event because no difference in cold target inhibition could be demonstrated with bFGF-treated cells. NK cytotoxicity has largely been attributed to the action of cytotoxins released from cytoplasmic granules. In a 51Cr release assay, bFGF-treated fibroblasts were insensitive to NK granules isolated from the RNK large granular lymphocyte leukemia. However, these same cells exhibited marked sensitivity to lysis in an 18-h adhesion assay normally utilized to detect TNF-alpha. With the use of this assay, a dose-dependent increase in sensitivity of bFGF-treated fibroblasts was observed, whereas quiescent fibroblasts were resistant to the action of isolated NK granules. Granule cytotoxicity was not caused by cytolysin/perforin because inactivation of granule hemolytic activity with CaCl2 did not affect fibroblast killing, and bFGF-treated cells were insensitive to purified cytolysin/perforin. This suggested that another granule associated cytotoxin was responsible for enhanced NK sensitivity of actively proliferating fibroblasts.
Sequential mechanisms of cyclophosphamide-induced skin allograft tolerance including the intrathymic clonal deletion followed by late breakdown of the clonal deletion.
Authors: Eto M , Mayumi H , Tomita Y , Yoshikai Y , Nishimura Y , Nomoto K 
Published: December 2022

Abstract
The cellular basis of the transplantation tolerance in a model system of BALB/c (Mls-1b) mice rendered cyclophosphamide (CP)-induced tolerant to DBA/2 (Mls-1a) skin allograft was investigated by assessing V beta 6+ T cells. From our results, three major mechanisms that are essential to the CP-induced skin allograft tolerance were sequentially elucidated. The first mechanism was destruction of donor-Ag-stimulated T cells in the periphery by CP treatment. The second mechanism was intrathymic clonal deletion of donor-reactive T cells, such as V beta 6+ T cells, correlating strongly with intrathymic mixed chimerism. The clonal deletion, however, was not always essential for the maintenance of the skin allografts, because DBA/2 skin survived even after the clonal deletion terminated and V beta 6+ T cells reappeared in the periphery of the recipient BALB/c mice. The third mechanism was generation of tolerogen-specific suppressor T cells, especially in the late stage of the tolerance. In contrast, the clonal anergy that is evidenced by the specific suppression of mixed lymphocyte reaction in the recipient BALB/c mice after injecting with DBA/2 spleen cells alone was not considered as a significant mechanism in prolonging skin allograft survival because such anergic mice showed accelerated rejection of the skin allografts. These results may suggest practical hierarchy of the mechanisms of CP-induced allograft tolerance.
T cell receptor delta-gene expression and diversity in the mouse spleen.
Authors: Ezquerra A , Cron R Q , McConnell T J , Valas R B , Bluestone J A , Coligan J E 
Published: December 2022

Abstract
Thirteen T cell hybridomas and two cell lines expressing gamma delta TCR were generated from B10 and B6 CD3+CD4-CD8- splenic T cells. At least three different types of gamma-chains (V gamma 2-C gamma 1, C gamma 2, and C gamma 4) were shown to be expressed in these cells. Analysis of V delta gene segment usage in these hybridomas was performed by Northern blot hybridizations using probes specific for the V delta 1 through V delta 6 gene families and electrophoretic analysis of polymerase chain reaction amplified DNA obtained using V region-specific oligonucleotide primers for the V delta gene families as well as for V alpha 10, V alpha 4, and V alpha 11. These analyses revealed that V delta 5 gene segments are used by a high percentage of splenic gamma delta CD4-CD8- T cells (53% of the cells in our panel). Other V delta segments expressed by our panel of cells were V delta 2, V delta 4, V delta 6, and V alpha 10, indicating that the V delta repertoire expressed in the spleen is similar, but possibly not identical to the adult thymus repertoire. Sequence analysis of the V-D-J joinings of the delta-chain messages revealed substantial diversity, indicating that the delta-chain repertoire expressed in peripheral lymphoid organs uses a significant portion of the potential diversity predicted for these chains. These results demonstrate that, in spite of the low numbers of gamma delta T cells in peripheral lymphoid organs, the diversity of their TCR is extensive enough to play an important role in the immune response.
Cross-linking Fc receptors on monocytes triggers IL-6 production. Role in anti-CD3-induced T cell activation.
Authors: Krutmann J , Kirnbauer R , Köck A , Schwarz T , Schöpf E , May L T , Sehgal P B , Luger T A 
Published: December 2022

Abstract
IL-6 is a multifunctional cytokine which is produced by a variety of cells. Therefore it was examined whether anti-CD3-induced T cell activation was associated with the induction of functionally relevant IL-6 in human monocyte accessory cells. Significantly increased amounts of IL-6 were detected in supernatants of anti-CD3-treated PBMC. Stimulation of FACS-sorted greater than 98% pure monocyte accessory cells, but not of highly purified T cells with anti-CD3, resulted in an increased IL-6 production. Furthermore, anti-CD3 significantly enhanced IL-6 mRNA expression in monocyte accessory cells. IL-6 production was not limited to anti-CD3, inasmuch as equivalent IL-6 stimulation could be achieved with a mouse IgG2a isotype control antibody. In contrast to solid phase-bound mouse IgG2a, the soluble form of this antibody failed to induce IL-6 secretion indicating a requirement for Fc gamma RI receptor cross-linking. Moreover, this property may be specific for the Fc gamma RI receptor inasmuch as mouse IgG1 antibodies binding to the Fc gamma RII receptor did not significantly enhance IL-6 production. The role of IL-6 being an additional signal in T cell activation was confirmed by the finding that an anti-IL-6 antiserum was able to suppress anti-CD3-induced T cell activation. These data indicate that binding of anti-CD3 to Fc gamma RI may generate an activation signal towards the monocyte accessory cell leading to the production and secretion of monocyte IL-6, which in turn augments T cell activation, and also may be relevant to a variety of antibody-mediated immune responses against viral and bacterial infections.
Engagement of the monocyte surface antigen CD14 induces lymphocyte function-associated antigen-1/intercellular adhesion molecule-1-dependent homotypic adhesion.
Authors: Lauener R P , Geha R S , Vercelli D 
Published: December 2022

Abstract
Murine anti-CD14 mAb which recognize different CD14 epitopes induced marked homotypic adhesion of normal human monocytes. Induction of aggregation by anti-CD14 mAb required Mg2+, occurred at an optimal temperature of 37 degrees C, but not at 4 degrees C, and exhibited a kinetics which differed from adhesion triggered by IFN-gamma and anti-CD43 mAb. Monocyte adhesion induced by anti-CD14 mAb required neither Fcy gamma R engagement nor cross-linking of CD14, because adhesion was induced by F(ab)'2 fragments, as well as by monovalent F(ab) fragments of anti-CD14 mAb. mAb to CD11a, CD18, and intercellular adhesion molecule-1 (ICAM-1), but not antibodies to CD11b and CD11c, inhibited monocyte adhesion induced by CD14 engagement. These results indicate that CD14-dependent adhesion is mediated by lymphocyte function-associated Ag-1/ICAM-1 interactions. This was confirmed by the absence of aggregation in anti-CD14-stimulated cells from a patient with leukocyte adhesion deficiency. Monocyte adhesion upon CD14 engagement was blocked by an inhibitor of protein kinases, sphingosine. This suggests that protein kinases play a role in the intracellular signaling pathway(s) which couple CD14 to lymphocyte function-associated Ag-1/ICAM-1.
Association between IL-6 and CD40 signaling. IL-6 induces phosphorylation of CD40 receptors.
Authors: Clark E A , Shu G 
Published: December 2022

Abstract
CD40 mAb at subsaturating doses inhibit the growth of transformants of the M12 murine cell line expressing intact full length CD40 molecules (M12/CD40+ cells) but do not inhibit the growth of two M12 transformants expressing either a mutant CD40 cDNA missing most of the cytoplasmic tail (CD40/tailless) or a mutant cDNA with a substitution at residue 234 (CD40/234A, Ala for Thr). Using these transformants, we tested a panel of cytokines for the ability to mimic CD40 mAb. rIL-6 behaved like CD40 mAb and inhibited the growth of M12/CD40+ cells but not of CD40/tailless or CD40/234A mutants. The effect of IL-6 on M12/CD40+ cells not only required intact CD40 including threonine 234 but also was specific because IL-6 mAb blocked the inhibitory activity. The M12/CD40+ cells responsive to IL-6 expressed greater than 300,000 CD40 molecules/cells but, like M12/CD40-controls, expressed only small numbers (less than 50/cell) of high affinity IL-6R, indicating that CD40 is not a receptor for IL-6. Nevertheless, IL-6 utilizes intact CD40 efficiently when it signals these cells: treatment of M12/CD40+ cells with IL-6 induced increased phosphorylation of CD40. Conversely, triggering CD40 on M12/CD40+ cells leads to IL-6 production. Similar effects were evident in human CD40+ B cells: IL-6 increased the phosphorylation of CD40 in the IL-6-responsive cell line, CESS, and CD40 mAb induced IL-6 production in activated human B cells. Thus, CD40 may function to receive and regulate IL-6-dependent signals in B cells.
Peptides generated from C-reactive protein by a neutrophil membrane protease. Amino acid sequence and effects of peptides on neutrophil oxidative metabolism and chemotaxis.
Authors: Shephard E G , Anderson R , Rosen O , Myer M S , Fridkin M , Strachan A F , De Beer F C 
Published: December 2022

Abstract
We have recently provided evidence that C-reactive protein (CRP) could act as an up-regulatable substrate for membrane-associated neutrophil serine protease(s). The resultant degradation of CRP yielded small soluble bioactive peptides that inhibit many of the proinflammatory functions of activated neutrophils and could oppose the tissue destructive potential of these cells. We report on the reverse phase HPLC separation of the small TCA-soluble peptides obtained when CRP is degraded with nonstimulated or PMA-stimulated neutrophils and purified neutrophil membranes. The amino acid sequence of seven peptides isolated from the CRP digest has been ascertained and synthetic peptides homologous to these sequences have been synthesized. Three of the synthetic peptides corresponding to residues 201-206 (CRP-III), 83-90 (CRP-IV), and 77-82 (CRP-V) of the intact protein were identified to significantly inhibit superoxide production from activated neutrophils at 50 microM whereas CRP-III and CRP-V in addition inhibited neutrophil chemotaxis at this concentration. These peptides act additively and their action likely involves the signal transduction pathways for neutrophil activation.
Down-regulation of mannose receptor activity in macrophages after treatment with lipopolysaccharide and phorbol esters.
Authors: Shepherd V L , Abdolrasulnia R , Garrett M , Cowan H B 
Published: December 2022

Abstract
We have investigated the effects of LPS and PMA on the expression of functional mannose receptors in rat bone marrow-derived macrophages. After 48 h of treatment with LPS (10 ng/ml) and PMA (100 nM), mannose receptor activity was reduced by 70 to 80%. The effect of these agents on receptor activity was not reversible, and activity continued to decline after the agents were removed. Pretreatment of cells with dexamethasone was effective in blocking the LPS/PMA-induced down-regulation. Serine protease inhibitors did not block the reduction in receptor activity, suggesting that proteolysis is not involved in receptor down-regulation. LPS/PMA treatment did not increase turnover of the receptor. Ligand uptake studies showed that the total capacity of the uptake system was reduced by 80%, although the Kuptake was unaffected. Binding of 125I-mannose-BSA to intact macrophages showed a 70% decrease in surface receptor activity after treatment with LPS/PMA. LPS/PMA treatment had no effect on total receptor synthesis as quantitated by immunoprecipitation of metabolically labeled receptor. However, binding of metabolically labeled receptor to mannose-Sepharose, and binding of 125I-mannose-BSA to immunoprecipitated receptor revealed that intracellular plus surface binding sites were reduced to approximately 30% after LPS/PMA treatment. These results suggest that LPS/PMA treatment of macrophages results in an inactivation of mannose receptors with no effect on receptor turnover or biosynthesis.
Adenosine and related compounds counteract tumor necrosis factor-alpha inhibition of neutrophil migration: implication of a novel cyclic AMP-independent action on the cell surface.
Authors: Sullivan G W , Linden J , Hewlett E L , Carper H T , Hylton J B , Mandell G L 
Published: December 2022

Abstract
Human rTNF-alpha (greater than or equal to U/ml) decreased PMN nondirected and directed migration to FMLP to approximately 50% of control. Adenosine (100 microM) almost completely restored hrTNF-inhibited migration (nondirected from 54 to 92% and directed migration to from 54 to 93% of control). The lowest concentration of adenosine that restored hrTNF-inhibited migration was 3 microM, and the adenosine analogue, 5'-(N-cyclopropyl)-carboxamido-adenosine (CPCA) was more potent than adenosine. Although CPCA binds to A2-receptors and stimulates adenylate cyclase, the reversal of hrTNF-inhibited chemotaxis was found to be independent of both PMN cAMP content and binding to A2-receptors, because neither 8-Br-cAMP nor pertussis adenylate cyclase restored hrTNF-inhibited PMN chemotaxis and the A2-receptor antagonist, 1,3-dipropyl-7-methylxanthine decreased CPCA stimulated cAMP but enhanced CPCA-restoration of hrTNF-inhibited chemotaxis. The effect of adenosine could be augmented by inhibition of adenosine uptake and decreased by adenosine deamination. Pentoxifylline, (3,7 dimethyl-1-[5 oxo-hexyl] xanthine), like adenosine also restored PMN chemotaxis inhibited by hrTNF. The adenosine receptor antagonist, 1,3-dipropyl-8(phenyl-p-acrylate)-xanthine (BW A1433U), decreased restoration of hrTNF-inhibited chemotaxis by CPCA or pentoxifylline. Thus, the inhibitory effect of hrTNF on PMN migration can be counteracted by adenosine, CPCA, pentoxifylline, and compounds that increase adenosine availability to the surface of the PMN. Inasmuch as an A1-selective agonist N6-cyclopentyladenosine was less active, and the action of the A2-selective agonist CPCA was enhanced by an A2-receptor antagonist, we hypothesize that neither A1 or A2 receptors are involved in adenosine restoration of hrTNF-inhibited chemotaxis. Further, increased cAMP, an A2-regulated event, does not cause the effect, and adenosine restoration of hrTNF-inhibited migration does not appear to be mediated by changes in PMN [F-actin], FMLP receptor expression, or cytosolic calcium. Hence, the restoration of hrTNF-inhibited chemotaxis is controlled by a novel cyclic AMP-independent action on the PMN surface.
The role of humoral immunity in Cryptosporidium spp. infection. Studies with B cell-depleted mice.
Authors: Taghi-Kilani R , Sekla L , Hayglass K T 
Published: December 2022

Abstract
Cryptosporidiosis has become an important infection in man, particularly among very young or immunocompromised individuals. Here, the protective role of antibody responses to Cryptosporidium was examined using a well established murine model of cryptosporidiosis. Although normal neonatal BALB/c mice exhibited good IgM and IgG serum antibody responses, no correlation could be drawn between the intensity of these responses and the severity or duration of cryptosporidiosis. Moreover, B cell-deficient (anti-mu-treated) neonatal BALB/c mice did not differ from untreated or normal rabbit Ig-treated, age-matched controls in the onset, peak, or duration of cryptosporidiosis. The apparent absence of a role for antibody in these self resolving infections was supported by the lack of susceptibility of anti-mu-treated adult BALB/c to attempted infection with doses of Cryptosporidium 10 times the dose required to infect 100% of normal (Ig producing) neonates. The results suggest that the role of specific in vivo antibody responses in the resolution of murine infection with this coccidian parasite is minor and that the likelihood of success for cryptosporidial vaccines aimed solely at enhancing in vivo antibody production may be limited.
Multiple nuclear factors interact with sequences within the J beta 2-C beta 2 intron of the murine T cell receptor beta-chain gene.
Authors: Mauxion F , Pray M G , Sen R 
Published: December 2022

Abstract
Identification of tissue-specific DNaseI hypersensitive sites in the TCR J beta 2-C beta 2 intron has suggested the presence of sequences involved in the regulation of gene expression. Therefore, we have searched for protein-DNA interactions within a 930-bp fragment derived from the J beta 2-C beta 2 intron by in vitro DNaseI protection experiments and electrophoretic mobility-shift assays. This analysis has revealed, in addition to a previously characterized NF-kappa B binding site, the presence of seven potential protein-DNA interaction sites within this fragment. Interestingly, they are clustered in the regions where in vivo T cell-specific nuclease hypersensitive sites have been previously identified. Binding sites for four potential transcription factors have been mapped precisely by methylation-interference experiments. Sequence comparisons show that one of them is homologous to the Y box present in the promoter regions of MHC class II genes. Identification of several protein-DNA interactions clustered within the J beta 2-C beta 2 intron and the presence of binding sites for two well-characterized transcription factors suggest a transcriptional regulatory function for this region.