bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential regulation of granulocyte-macrophage colony-stimulating factor gene expression in human corneal cells by pro-inflammatory cytokines.
Authors: Cubitt C L , Lausch R N , Oakes J E 
Published: December 2022

Abstract
Neutrophils and Langerhans cells participate in inflammatory reactions within the human cornea. Because granulocyte-macrophage (GM)-CSF is a chemotactic and activating factor for these two cell types, we investigated whether this cytokine is produced by human corneal epithelial cells and corneal fibroblasts. Cultures of each cell type were exposed to increasing concentrations of IL-1 alpha or TNF-alpha. Culture supernatants were assayed for GM-CSF by using ELISA and cytokine mRNA levels were monitored by using reverse transcriptase-PCR. IL-1 alpha treatment of both cell types resulted in the appearance of GM-CSF mRNA and the production of &gt; 480 pg protein/10(6) cells. However, TNF-alpha treatment yielded divergent results. Stimulation of epithelial cells with TNF-alpha resulted in the appearance of &gt; 560 GM-CSF mRNA molecules per cell and production of &gt; 1300 pg GM-CSF/10(6) cells. In contrast, stimulation of corneal fibroblasts resulted in &lt; 16 GM-CSF mRNA molecules/cell and &lt; 60 pg GM-CSF/10(6) cells. Binding studies with 125I-labeled TNF-alpha revealed that corneal fibroblasts had as many receptor sites as did corneal epithelial cells. Furthermore, corneal fibroblasts could respond to TNF-alpha-receptor-mediated signal transduction because they produced nanogram amounts of IL-6 after being treated with this cytokine. The results suggest that both cell types synthesize GM-CSF in response to IL-1 alpha, but that only corneal epithelial cells produce significant amounts of GM-CSF after TNF-alpha exposure. Differences in the responses of the two cell types to TNF-alpha may reflect a means of limiting accumulation of neutrophils and Langerhans cells and, thus, minimize corneal damage.
Lipolysaccharide-induced monocyte retention in the lung. Role of monocyte stiffness, actin assembly, and CD18-dependent adherence.
Authors: Doherty D E , Downey G P , Schwab B , Elson E , Worthen G S 
Published: December 2022

Abstract
Blood monocytes and monocyte-derived macrophages accumulate in the lungs and can modulate pulmonary inflammatory and reparative processes through their elaboration of cytokines and growth factors. Endotoxemia, often a prelude to acute lung injury, induces a monocytopenia, likely resulting from monocyte accumulation in the lung. We hypothesized that LPS would induce monocyte lung retention by increasing monocyte stiffness and thereby diminishing the cell's ability to deform and transit the narrow pulmonary capillary network, and that LPS would induce CD18-dependent adhesion of monocytes to endothelium, prolonging their retention. LPS induced a rapid and concentration-dependent increase in human monocyte stiffness, net filamentous actin assembly, and retention in a filtration model of pulmonary capillaries. These LPS-induced responses were dependent on the integrity of actin filaments in that cytochalasin D, an agent that disrupts filamentous actin assembly, attenuated each of these processes. LPS induced CD18-dependent and -independent human monocyte adhesion to unstimulated human endothelial cell monolayers. In vivo, rabbit monocytes were retained in the lungs of animals rendered endotoxemic. Pretreatment of monocytes ex vivo with LPS enhanced their lung retention suggesting that LPS was acting directly on monocytes. Initial lung retention during endotoxemia was attenuated by inhibiting monocyte F-actin assembly with cytochalasin D. Anti-CD18 Abs caused a slight decrease in initial retention of monocytes, but led to a 90% inhibition of retention by 2 h. Control IgG had no effect. These data suggest that the initial retention of monocytes in the lung during endotoxemia is dependent on alterations in their stiffness and assembly/organization of F-actin, and that CD18-dependent adhesive mechanisms prolong monocyte retention in the lung during this process.
Regulation of C1q receptor expression on human polymorphonuclear leukocytes.
Authors: Jack R M , Lowenstein B A , Nicholson-Weller A 
Published: December 2022

Abstract
The C1q receptor (C1qR) is expressed on a variety of cells, including polymorphonuclear leukocytes (PMN), in which stimulation by the C1qR leads to activation as measured by superoxide production. To investigate the expression and modulation of the C1qR on PMN, the binding of biotinylated C1q to PMN in suspension was measured by flow cytometry. Biotinylated C1q bound in a saturable and specific manner to PMN and the use of low ionic strength buffers enhanced binding. Covalent coupling of C1q to Sepharose beads allowed the affinity precipitation of a single 125-kDa band from surface iodinated PMN. The apparent molecular mass of the C1qR increased to 135 kDa upon reduction. Freshly isolated PMN had a uniform expression of C1qRs and phorbol myristate acetate induced a unimodal up-regulation of receptors. The inflammatory peptide FMLP rapidly up-regulated receptors by up to fivefold, and the high level of expression remained constant over 45 min. Taxol inhibited the FMLP induction of C1qR up-regulation, indicating that the ability to move the intracellular stores of C1qR depends on normal microtubule functioning. Thus, the C1qR is a constitutively expressed protein of the human PMN plasma membrane and it is rapidly up-regulated from a discrete intracellular pool of preformed molecules with the same kinetics as CR1 and CR3. It is likely that the C1qR is a component of the PMN complement receptor exocytic vesicle (CREV), in which CR1 and CR3 are also stored.
IL-7 stimulates CSF-induced proliferation of murine bone marrow macrophages and Mac-1+ myeloid progenitors in vitro.
Authors: Jacobsen F W , Veiby O P , Jacobsen S E 
Published: December 2022

Abstract
The role of IL-7 as an important stimulator of the growth of B and T cell precursors, as well as mature T cells, is well established. In contrast, the role of IL-7 in myelopoiesis has not been characterized thoroughly, and thus, IL-7 has been regarded as a lymphoid lineage-restricted cytokine. However, we have recently reported that IL-7 enhanced CSF-induced myeloid proliferation of primitive murine hematopoietic (Lin-Sca-1+) progenitors, whereas IL-7 did not affect significantly the proliferation of a population of more mature (Lin-) progenitors. The present study was initiated to investigate further whether IL-7 might affect CSF-induced proliferation of subpopulations of committed myeloid progenitors as well as mature bone marrow macrophages. IL-7 enhanced macrophage colony-stimulating factor (CSF-1)-induced colony formation of single bone marrow macrophages 90%, whereas IL-7 alone had no effect. Furthermore, IL-7, in a concentration-dependent manner, increased the proliferation of mononuclear cells expressing the Mac-1 Ag (Mac-1+ mononuclear cells (MNC); CD11b) up to fivefold in response to CSF-1, granulocyte macrophage-CSF (GM-CSF), or IL-3. In contrast, no effect of IL-7 was observed on Mac-1- MNC. The synergistic effect of IL-7 on Mac-1+ MNC was caused by an increase in macrophage colonies (CFU-M) and mixed granulocyte-macrophage colonies (CFU-GM), whereas the total number of granulocyte colonies (CFU-G) was not affected. This suggests that IL-7 can provide proliferative signals to Mac-1+ progenitors with a macrophage potential, but not to progenitors committed to pure granulocyte differentiation.
Tyrosine phosphorylation in activated human neutrophils. Comparison of the effects of different classes of agonists and identification of the signaling pathways involved.
Authors: Rollet E , Caon A C , Roberge C J , Liao N W , Malawista S E , McColl S R , Naccache P H 
Published: December 2022

Abstract
The tyrosine phosphorylation responses initiated in human neutrophils by soluble and particulate agonists were characterized. Chemotactic factors, hematopoietic growth factors, and inflammatory microcrystals stimulated in a time- and concentration-dependent manner the tyrosine phosphorylation of distinct patterns of substrates: pp120, pp85, pp70, and pp60 in the case of chemotactic factors; pp155, pp130, pp120, pp85, pp60, and pp40 in the case of granulocyte macrophage-CSF; and pp130, pp120, pp70, and pp60 in the case of monosodium urate (MSU) crystals. Several of the single bands on one-dimensional blots (including pp40, pp70, and pp120) could be resolved into multiple spots on two-dimensional gels. The responses of several other chemotactic factors resembled those of FMLP. Cytokineplasts retained the capacity to respond to FMLP, granulocyte-macrophage-CSF, or MSU crystals with a stimulation of tyrosine phosphorylation, and contained the major substrates detected in intact neutrophils. Several unrelated tyrosine kinase inhibitors (herbimycin A, genistein, and erbstatin) strongly diminished the tyrosine phosphorylation response to chemotactic factors. Pertussis toxin abrogated the tyrosine phosphorylation response to FMLP, whereas protein kinase C (Ro 21-8220, chelerithryn) inhibitors were without effect. Chelation of intracellular calcium attenuated the tyrosine phosphorylation response to FMLP. These results indicate that G proteins play a crucial role in the coupling of chemotactic factor receptors to tyrosine phosphorylation and that this coupling occurs in parallel to that of phospholipase C. These results also underline the complexity of the transduction pathways implicated in the initiation of tyrosine phosphorylation.
A potential role for antigen selection in the clonal evolution of Burkitt's lymphoma.
Authors: Jain R , Roncella S , Hashimoto S , Carbone A , Francia di Celle P , Foa R , Ferrarini M , Chiorazzi N 
Published: December 2022

Abstract
Burkitt's lymphoma (BL) is a monoclonal lymphoproliferative disorder characterized by the presence of specific chromosomal translocations that involve the c-myc proto-oncogene. Two subtypes of BL exist (endemic and sporadic) that differ in the prevalence of EBV genome expression. Although EBV infection may promote cellular proliferation in endemic BL, little is known about the forces that drive clonal expansion and evolution in the majority of EBV-negative sporadic BL. This study on an EBV-negative sporadic BL cell line derived from an AIDS patient provides evidence that antigenic stimulation may play a role in the development and/or expansion of such tumors. This cell line (BRG-P) contained a series of cellular clones that elaborated both IgM and IgA. Southern blot analyses of the line and its sublines indicated that both the IgM+ and IgA+ cells had identical c-myc and Ig JH gene rearrangements, indicating that they were derived from a common precursor, some of which eventually underwent an isotype switch. Ig VH gene sequence analyses of 21 molecular clones derived from the parental BRG BL line and two of its sublines demonstrated that all the clones used the same VH3 gene. Five unique intraclonal variants were identified at four distinct nucleotide positions (125, 161, 355, 375), which undoubtedly represented somatic mutations. Four of these five mutations occurred within complementary determining regions; all resulted in amino acid replacements. Moreover, an identical G to A nucleotide substitution that resulted in an identical amino acid change occurred at two distinct points in clonal evolution that were separated by the isotype class switch. Thus, the locations and types of the VH gene mutations, together with the occurrence of an isotype switch, are highly suggestive of an ongoing role for Ag stimulation and selection in the evolution of the malignant clone.
Developmentally regulated expression of a murine receptor-type protein tyrosine phosphatase in the thymus.
Authors: Ogata M , Sawada M , Kosugi A , Hamaoka T 
Published: December 2022

Abstract
Reversible phosphorylation of tyrosine residues plays a crucial regulatory role in various cellular events, including differentiation and proliferation of lymphocytes. Here, we report the isolation of a murine receptor-type protein tyrosine phosphatase (PTP), mRPTP-sigma, which is expressed in both immature thymocytes and stroma cells. At least two alternatively spliced transcripts of mRPTP-sigma (T and B) were observed. mRPTP-sigma T was the dominant form in the thymus and had three Ig-like and eight fibronectin type III-like domains in the extracellular portion. mRPTP-sigma T was almost identical with RPTP-sigma/PTP NE-3/PTP-P1/CPTP1, a PTP recently cloned from rat brain, except that RPTP-sigma/PTP NE-3/PTP-P1 was about 400 amino acids shorter than mRPTP-sigma T. mRPTP-sigma B, the second form of mRPTP-sigma, was dominant in the brain and was most likely the murine counterpart of RPTP-sigma/PTP NE-3/PTP-P1. In the developing thymocytes, the expression of mRPTP-sigma was high in double negative (CD4-CD8-), low in double positive (CD4+CD8+), and marginal in single positive (SP; CD4+CD8- or CD4-CD8+) subpopulations. No upregulation of mRPTP-sigma was observed in the spleen cells stimulated with Con A. Developmental regulation of mRPTP-sigma expression suggests its involvement in the control of T lymphocyte differentiation.
A predominant viral epitope recognized by T cells from the periphery and demyelinating lesions of SJL/J mice infected with Theiler's virus is located within VP1(233-244).
Authors: Yauch R L , Kim B S 
Published: December 2022

Abstract
The intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV) into susceptible strains of mice results in a chronic, immune-mediated demyelinating disease that shares many features with human multiple sclerosis. As with human MS, T lymphocytes seem to be critically important for the pathogenesis of this virally induced, demyelinating disease. Therefore, determining the fine specificity of the T cell response may be essential for elucidating the mechanism(s) involved in demyelination. By using fusion proteins and synthetic peptides, we have initially identified a region within the amino acid residues 233 to 250 of the VP1 capsid protein of Theiler's virus that is recognized by T cells from either TMEV-immunized or TMEV-infected, demyelination-susceptible SJL/J mice. A T lymphocyte precursor frequency analysis indicates that a major TMEV-reactive T cell population in the periphery of virus-infected mice recognizes this VP1 region. The fine epitope specificity has been further determined to be within VP1(233-244) using additional synthetic peptides. VP1(233-244)-specific T cells seem to represent a significant population of TMEV-reactive T lymphocytes within the demyelinating lesions, because such T cells have been cloned from the spinal cords of infected mice. Interestingly, all TMEV-specific T cell clones derived from the demyelinating lesions, regardless of epitope specificity, produce IFN-gamma on stimulation and thus may play a critical role in the recruitment and activation of inflammatory cells leading to demyelination. Taken together, these data suggest that a T cell response against VP1(233-244) is involved in the pathogenesis of TMEV-induced demyelinating disease.
Organization of the transcription factor binding sites in the kappa Ig intron enhancer. Effects of position, orientation, and spacing.
Authors: Schanke J T , Van Ness B G 
Published: December 2022

Abstract
The kappa Ig intron enhancer is comprised of multiple sequence motifs known to bind trans-acting factors that activate gene expression. A species comparison reveals a high level of conservation of the organization of the transcription factor binding sites within the enhancer. The importance of the conserved organization of the kappa intron enhancer was examined by using topologic mutations that disrupt the position, orientation, and spacing of individual binding sites within the enhancer. The effects of these changes were monitored by their effects on reporter gene activity at two distinct stages of B cell development. Previously, mutational analysis indicated the kappa B and kappa E2 sequence motifs to be the most crucial sites for intron enhancer function. We have demonstrated that intron enhancer activity is dependent on the position of the kappa B and kappa E2 sequence motifs within the enhancer. Intron enhancer function is, however, independent of kappa B and kappa E2 binding site orientation and is flexible in spacing requirements among binding sites.
IFN-alpha 1 gene expression into a metastatic murine adenocarcinoma (TS/A) results in CD8+ T cell-mediated tumor rejection and development of antitumor immunity. Comparative studies with IFN-gamma-producing TS/A cells.
Authors: Ferrantini M , Giovarelli M , Modesti A , Musiani P , Modica A , Venditti M , Peretti E , Lollini P L , Nanni P , Forni G 
Published: December 2022

Abstract
Cells from a spontaneous, invasive, and metastasizing mouse mammary adenocarcinoma (TS/A-pc) were transfected with a retroviral vector containing the mouse IFN-alpha 1 gene. TS/A clones secreting varying amounts of IFN-alpha 1 were isolated and their tumorigenicity was evaluated after s.c. or i.v. injection into immunocompetent BALB/c mice. Almost all of the IFN-alpha-secreting TS/A clones failed to grow in a high percentage of mice or formed small tumors after a long latency time, whereas TS/A-pc or transfection control cells always grew into large s.c. tumors. Rejection was mainly mediated by CD8+ T lymphocytes and partially by polymorphonuclear cells, as demonstrated by selective immunosuppression experiments and histologic and ultrastructural data. After rejection, a significant portion of mice displayed an immune resistance to the subsequent challenge with TS/A-pc. When the metastatic ability of IFN-alpha-secreting clones was compared with that of previously characterized IFN-gamma-secreting TS/A clones, it was found that the expression of IFN-alpha into TS/A tumor cells resulted in a potent inhibition of metastases formation, whereas IFN-gamma expression either did not affect or even enhanced the metastatic behavior of TS/A cells. These results provide strong evidence for the usefulness of IFN-alpha-producing tumor cells for the development of gene therapy strategies and vaccines against metastatic tumors.
Activation of LPS-inducible genes by the antitumor agent 5,6-dimethylxanthenone-4-acetic acid in primary murine macrophages. Dissection of signaling pathways leading to gene induction and tyrosine phosphorylation.
Authors: Perera P Y , Barber S A , Ching L M , Vogel S N 
Published: December 2022

Abstract
The synthetic flavone analogue 5,6-dimethylxanthenone-4-acetic acid (5,6-MeXAA) has shown promise as an antitumor agent and is currently a candidate for clinical trials. Because 5,6-MeXAA has been shown in a murine macrophage and a human myelomonocytic cell line to induce TNF-alpha mRNA and to activate macrophages to become tumoricidal, actions that are shared with bacterial LPS, we sought to determine the level of LPS mimetic activity exhibited by this low m.w. macrophage-activating agent. To elucidate its mechanisms of action, the capacity to induce a panel of LPS-inducible genes was assessed. 5,6-MeXAA was found to induce a subset of LPS-inducible genes within the panel in both Lpsn and Lpsd primary murine macrophages. Of the six LPS-inducible genes examined, there was marked induction of IP-10, D8, and D3; low induction of TNF-alpha gene expression; and insignificant induction of TNFR-2 and IL-1 beta genes. 5,6-MeXAA was also found to be a potent inducer of IFNs in macrophages of both strains, and of increased expression of the genes that encode the IFN regulatory factors IRF-1, IRF-2, and ICSBP. In contrast with LPS, 5,6-MeXAA failed to induce significantly any of the 40- to 45-kDa tyrosine phosphoproteins induced by LPS. These data suggest that 5,6-MeXAA shares with LPS certain biochemical pathways that lead to gene induction and allow for the additional dissection of the relationship of tyrosine phosphorylation and the expression of specific genes.
Antigen presentation and assembly by mouse I-Ak class II molecules in human APC containing deleted or mutated HLA DM genes.
Authors: Brooks A G , Campbell P L , Reynolds P , Gautam A M , McCluskey J 
Published: December 2022

Abstract
The behavior of mouse I-Ak molecules was studied in the human Ag presentation mutants T2 and 9.5.3, which contain deleted or mutated HLA DM genes. HLA class II molecules expressed by these APC are defective in presentation of native Ag and are mostly complexed with class II-associated invariant chain peptides (CLIP). In contrast to human class II molecules, a significant proportion of mouse I-Ak molecules expressed in T2 and 9.5.3 were associated with antigenic peptides, indicating that I-Ak/peptide assembly is possible in the absence of the Dm proteins. Thus, the presentation of determinants derived from hen egg lysozyme (HEL), keyhole limpet hemocyanin, and conalbumin was normal in 9.5.3Ak and a conalbumin determinant was presented normally by T2.Ak. However, the keyhole limpet hemocyanin determinant was not presented by T2.Ak, and HEL46-61 was only presented at a low level by these APC. SDS-stable, dimeric I-Ak molecules were expressed by both T2.Ak and 9.5.3Ak and formed late in their intracellular transport. Presentation of HEL46-61 was partially inhibited by disrupting vacuolar acidification in 9.5.3Ak, consistent with I-Ak/peptide assembly in a post-Golgi endosomal compartment. Accordingly, Dm is not an obligatory requirement for MHC class II/peptide assembly. We propose that Dm influences the displacement of CLIP from recently synthesized class II molecules, a process that is likely to be less critical for I-Ak because of its low affinity for CLIP.
Differential regulation of proto-oncogenes c-jun and c-fos in T lymphocytes activated through CD28.
Authors: Chatta G S , Spies A G , Chang S , Mize G J , Linsley P S , Ledbetter J A , Morris D R 
Published: December 2022

Abstract
The T cell surface molecule CD28 binds to ligands on accessory cells and APCs, playing an important costimulatory role in the response of T cells to Ags. Our knowledge of the intracellular signaling pathways coupled to this receptor is incomplete. In addition to activation of phospholipase C gamma 1, ligation of this receptor also seems to activate a calcium-independent, CD28-specific pathway. In this paper, we report that cross-linking of CD28 (but not CD2, CD5, LFA-1, or CD7) leads to an elevation of c-jun mRNA, with only minimal activation of c-fos expression. CD28-dependent induction of c-jun expression requires protein tyrosine kinase activity, but does not depend on activation of a phorbol ester-responsive protein kinase C or elevation of cytosolic calcium. Furthermore, CD28-dependent elevation of c-jun mRNA does not appear to be mediated at the level of mRNA stability. A mechanism is suggested whereby expression of c-jun and junB, in the absence of members of the fos family, can prevent inappropriate activation of T cells caused by ligation of CD28 in the absence of a specific antigenic stimulus.