bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effects of macrophage- and granulocyte-macrophage colony-stimulating factors on cytokine gene expression during rat alveolar macrophage differentiation into multinucleated giant cells (MGC): role for IL-6 in type 2 MGC formation.
Authors: Lemaire I , Yang H , Lafont V , Dornand J , Commes T , Cantin M F 
Published: December 2022

Abstract
Macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage (GM)-CSF stimulate the differentiation of rat alveolar macrophages (AM) into multinucleated giant cells (MGC) with distinct phenotypes (type 1 and type 2 MGC). In the present study, we analyzed the profile of cytokine gene expression induced respectively, by M-CSF and GM-CSF during rat AM differentiation using reverse transcription-PCR. Enhanced mRNA expression for IL-1alpha, TNF-alpha, and TGF-beta1 was observed 3 h after treatment with M-CSF (50 U/ml) or GM-CSF (50 U/ml). In contrast, IL-6 mRNA expression was increased by GM-CSF but not M-CSF. Kinetic analysis indicated that GM-CSF stimulated IL-6 expression early (1.5 h), with maximal effect observed at 24 h and up to 5 days thereafter. Increased mRNA levels for IL-6 were associated with higher IL-6 activity in the culture media of differentiating AM. IL-6 activity was stimulated 3 h after treatment with GM-CSF and increased with time (up to 5 days). Interestingly, addition of exogenous IL-6 (20-100 ng/ml) alone or in combination with GM-CSF to AM cultures increased slightly and selectively the formation of MGC with type 2 phenotype. Conversely, neutralization of endogenous IL-6 during AM differentiation into MGC inhibited significantly (up to 50%) the formation of type 2 MGC. These results suggest a role for IL-6 in the formation of type 2 MGC and provide some insights into the mechanisms of MGC formation and the processes that regulate it positively.
Calcium ionophore-induced secretion from mast cells correlates with myosin light chain phosphorylation by protein kinase C.
Authors: Ludowyke R I , Scurr L L , McNally C M 
Published: December 2022

Abstract
Rat basophilic leukemia mast cells (RBL-2H3) secrete histamine when activated by Ag. This secretion correlates with increased phosphorylation of myosin light chain by protein kinase C (PKC). Calcium ionophores (A23187) also elicit secretion, which is enhanced by PMA. To analyze the roles of Ca2+ and PKC in the secretory process, A23187-induced myosin light chain phosphorylation was examined in the presence and absence of PMA. A23187-induced secretion correlated best with myosin light chain phosphorylation by PKC, not with phosphorylation by myosin light chain kinase (MLCK). A23187 induced the translocation to membranes of the alpha, beta, delta, and epsilon isozymes of PKC. PMA not only increased the phosphorylation of myosin light chains at PKC-specific sites (Ser1 and Ser2) but also at sites attributed to MLCK (Ser19 and Thr18-Ser19). A23187 plus PMA induced higher levels of secretion concomitantly with increased myosin light chain phosphorylation at the PKC-specific sites. However, there was little correlation between the translocation of specific PKC isozymes and the phosphorylation of myosin light chains by PKC. Activation induced a novel triphosphorylated form of myosin light chain with a higher level of phosphorylation at the diphosphorylated MLCK sites. Quantitation of A23187 plus PMA-induced myosin light chain phosphorylation revealed that phosphorylation at PKC sites increased from zero to 0.35 mol/mol, was little changed at the monophosphorylated MLCK site (0.30 mol/mol), and increased from zero to 0.06 mol/mol at the diphosphorylated MLCK sites. Therefore, Ca2+-induced secretion correlates best with myosin light chain phosphorylation by PKC, and diphosphorylation by MLCK is unlikely to contribute to secretion.
Recruitment of lymphoblasts derived from peripheral and intestinal lymph to synovium and other tissues in normal rats and rats with adjuvant arthritis.
Authors: Spargo L D , Hawkes J S , Cleland L G , Mayrhofer G 
Published: December 2022

Abstract
Recruitment of [125I]iododeoxyuridine-labeled syngeneic lymphoblasts from thoracic duct (TD) lymph into periarticular tissues has been examined after intravenous administration to normal rats and to rats with adjuvant-induced arthritis. Uptake of label was observed in the inflamed paws of arthritic rats and cells were located in synovium and periarticular bone marrow by autoradiography. Uptake was greater with lymphoblasts from donors in the late prodromal phase of adjuvant-induced arthritis (arthritic donors) than from normal donors. With arthritic donors, recruitment of lymphoblasts from TD lymph was greater than from mesenteric duct lymph, suggesting that most of the joint-seeking lymphoblasts in arthritic rats arose in peripheral lymphoid tissues. Lymphoblasts from arthritic donors were also detected in the synovium of paws from normal rats. Recovery of lymphoblasts was monitored in other tissues; this revealed, in arthritic recipients, competition among extra-articular sites of inflammation (adjuvant injection site, draining lymph nodes, and lymph nodes draining affected joints), the lungs, and the inflamed synovium for recruitment of lymphoblasts from arthritic donors. In contrast, while some lymphoblasts from normal donors were recruited to inflamed joints, the small intestine was the main site of recruitment. The results reflect the known propensity of T lymphoblasts generated in peripheral lymphoid tissues to enter inflamed tissues. However, some mesenteric duct lymphoblasts also entered inflamed synovium. The observed pattern of recruitment of lymphoblasts to synovium is pertinent to the pathogenesis of arthritis, the potential roles of arthritogenic and "bystander" lymphocytes and the known links between the joints and inflammation in the intestine.
CD100 is associated with CD45 at the surface of human T lymphocytes. Role in T cell homotypic adhesion.
Authors: Herold C , Elhabazi A , Bismuth G , Bensussan A , Boumsell L 
Published: December 2022

Abstract
CD100 is a 150-kDa human surface glycoprotein implicated in T cell activation. Using BB18 and BD16 mAbs to two discrete epitopes of the CD100 molecule, we have shown previously that triggering the CD100 molecule through the BB18 epitope is comitogenic with PMA, whereas it lacks a detectable effect on CD2- and CD3-induced PBMC proliferation. Conversely, triggering the CD100 molecule through the BD16-defined epitope only exerts an effect on CD2- and CD3-induced PBMC proliferation. In the present study, we investigated the molecular relationship between CD100 and another surface structure involved in human T cell proliferation, the CD45 phosphatase. We show in this study that CD100 is associated with CD45 and that this association has functional significance. The association was demonstrated using coimmunoprecipitation and detection of CD45 enzymatic PTPase activity. Furthermore, we show that the association is increased during T cell activation and that triggering CD45 molecules through discrete epitopes induces the down-modulation of CD100 molecules at the cell surface. Interestingly, we demonstrate that this modulation could be attributed to the shedding of a soluble form of CD100 in the culture supernatant. Finally, one of the functional consequences of this T cell activation-induced CD100-CD45 association is revealed by the finding that CD100 mAbs have an effect on CD45-induced T cell aggregation.
delta opioid receptor expression is induced by concanavalin A in CD4+ T cells.
Authors: Miller B 
Published: December 2022

Abstract
Expression of delta opioid receptor mRNA in CD4+ T cells purified from Con A-stimulated murine splenocytes was demonstrated by reverse transcription-PCR and sequencing of the PCR products. mu and kappa opioid receptor mRNAs were not detected. Similar results were obtained in a single isolation of CD8+ T cells from Con A-stimulated splenocytes. mRNA for the delta opioid receptor was not detected in CD4+ T cells purified from either freshly isolated splenocytes or splenocytes cultured without Con A, and incubation of purified CD4+ T cells with Con A did not induce delta opioid receptor mRNA. It appears that quiescent CD4+ T cells do not express classic opioid receptors, but the delta-type receptor can be induced upon activation.
Impaired immune responses toward alloantigens and tumor cells but normal thymic selection in mice deficient in the beta2 integrin leukocyte function-associated antigen-1.
Authors: Shier P , Otulakowski G , Ngo K , Panakos J , Chourmouzis E , Christjansen L , Lau C Y , Fung-Leung W P 
Published: December 2022

Abstract
We have generated mice deficient in the beta2 integrin LFA-1 by targeted disruption of the CD11a gene in embryonic stem cells. In vitro LFA-1 -/- cells exhibit a delayed proliferative response toward alloantigens in the MLR. In vivo the host-vs-graft reaction toward injected allogeneic cells is also reduced. Alloantigen-specific CTLs generated from LFA-1 -/- mice are impaired in their cytotoxic activity toward allogeneic spleen cells as well as cell line targets. The proliferative response of LFA-1 -/- splenocytes following stimulation by LPS, PMA plus ionomycin, or immobilized anti-CD3epsilon mAb is normal, but Con A-stimulated proliferation is greatly diminished. We observe typical edema formation in a delayed type hypersensitivity reaction to SRBC with normal extravasation of leukocytes and demonstrate recruitment of neutrophils to an LPS-induced inflammatory site in these mice, suggesting that LFA-1 does not play an essential role in lymphocyte homing and leukocyte extravasation. We further show that LFA-1 -/- mice are susceptible to metastasis of B16 melanoma tumors, although their in vitro NK cell activity appears normal. A study of LFA-1 -/- mice expressing transgenic TCRs indicates that thymic maturation and selection of T cells are unaffected by the loss of LFA-1. Our results indicate that LFA-1 is important for alloantigen-triggered T cell proliferation and cytotoxicity, for Con A stimulation of T cells, and in tumor rejection. It does not appear to play an essential role in lymphocyte homing and leukocyte extravasation or in T cell maturation and selection in the thymus.
Differential activation of human platelets induced by Fc gamma receptor II cross-linking and by anti-CD9 monoclonal antibody.
Authors: Qi R , Ozaki Y , Kuroda K , Asazuma N , Yatomi Y , Satoh K , Nomura S , Kume S 
Published: December 2022

Abstract
Platelet activation induced by anti-CD9 mAb, which depends upon Fc gammaRII, has been considered to be similar to that induced by Fc gammaRII cross-linking. In this work, we present several lines of evidence to suggest that the mode of platelet activation induced by anti-CD9 mAb is distinct from that induced by Fc gammaRII cross-linking. Ca2+ release from intracellular Ca2+ stores induced by anti-CD9 mAb depended almost totally upon thromboxane A2 production and released ADP, whereas that induced by Fc gammaRII was affected only minimally by these factors. Fc gammaRII cross-linking induced Ca2+ channel opening, which is dependent upon the depletion of intracellular Ca2+ stores. In contrast, anti-CD9 mAb appeared to directly open Ca2+ channels, irrespective of intracellular Ca2+ stores (Kuroda et al., 1995. J. Immunol. 155: 4427). The Ca2+ requirement for the Ca2+ channels opened by Fc gammaRII cross-linking was also distinct from that induced by anti-CD9 mAb. The early phase of Fc gammaRII tyrosine phosphorylation was dependent upon thromboxane A2 production with anti-CD9 mAb-induced activation, whereas that of Fc gammaRII cross-linking was not. p72(syk) and p53/56(lyn) appeared to associate with Fc gammaRII in platelet activation induced by Fc gammaRII cross-linking, whereas there was little, if any, association between Fc gammaRII and these tyrosine kinases in anti-CD9 mAb-induced activation. Piceatannol, a selective inhibitor of p72(syk), enhanced Fc gammaRII tyrosine phosphorylation induced by Fc gammaRII cross-linking, whereas it attenuated the process in anti-CD9 mAb-induced platelet activation. It is suggested that the regulatory mechanism of Fc gammaRII tyrosine phosphorylation differs between these two modes of platelet activation.
The length of treatment determines whether IFN-beta prevents or aggravates experimental autoimmune encephalomyelitis in Lewis rats.
Authors: Ruuls S R , de Labie M C , Weber K S , Botman C A , Groenestein R J , Dijkstra C D , Olsson T , van der Meide P H 
Published: December 2022

Abstract
The mechanism of action underlying the beneficial effect of IFN-beta in multiple sclerosis (MS) is not understood. To date, little information is available on the effects of IFN-beta in experimental autoimmune encephalomyelitis (EAE), the animal correlate of the human disease MS. Therefore, we investigated the effects of recombinant rat IFN-beta (rrIFN-beta) on EAE in Lewis rats with emphasis on a treatment regimen during the paralytic phase of the disease. The results indicated that rrIFN-beta dose-dependently inhibited disease activity with complete prevention at a s.c. dose of 300,000 U/day, provided that treatment was continued for 3 wk. Discontinuation of treatment on day 17 postimmunization resulted in a protracted and relapsing disease course with strongly enhanced clinical severity. Detailed immunohistology of central nervous system (CNS) tissue of protected animals revealed an almost complete absence of CNS lesions and a &gt;90% reduction in the number of infiltrating leukocytes. Accordingly, isolation of mononuclear cells from spinal cord tissue of successfully treated EAE rats revealed a reduction of approximately 95% in the number of cells that produce IFN-gamma in response to the encephalitogenic peptide MBP63-88. Furthermore, rrIFN-beta significantly enhanced serum corticosterone levels, which showed an inverse relationship with disease activity. We show that rrIFN-beta can have both beneficial and detrimental effects on disease activity dependent on the timing and the duration of treatment. Beneficial effects on EAE are associated with inhibition of the extravasation of blood-derived mononuclear cells in the CNS.
The anti-beta2-glycoprotein I activity in human anti-phospholipid syndrome sera is due to monoreactive low-affinity autoantibodies directed to epitopes located on native beta2-glycoprotein I and preserved during species' evolution.
Authors: Tincani A , Spatola L , Prati E , Allegri F , Ferremi P , Cattaneo R , Meroni P , Balestrieri G 
Published: December 2022

Abstract
To characterize the reactivity pattern of Abs directed to beta2-glycoprotein I (anti-beta2GPI) in patients with anti-phospholipid syndrome, we have purified anti-beta2GPI Abs by affinity chromatography using the IgG fractions from sera of five different anti-phospholipid syndrome patients. Affinity-purified anti-beta2GPI were shown to be representative of Abs found in human sera because their activity could be virtually abolished from the IgG preparations after repeated absorptions on immobilized human beta2GPI column. Our results show that affinity-purified anti-beta2GPI: 1) do react with beta2GPI in the absence of any phospholipid, as demonstrated by the lack of phosphorus contaminant in the employed reagents, as well as by their comparable binding activity before and after extensive delipidation procedure; 2) can recognize beta2GPI regardless of its origin from different animal species; 3) are able to bind soluble beta2GPI with a mean Kd value of 4.65 x 10(-6) M (range 3, 4-7, 2 x 10(-6) M); 4) significantly enhance their binding avidity when beta2GPI is linked to a solid support; and 5) appear to be mainly monoreactive autoantibodies. In conclusion, we have shown that human polyclonal anti-beta2GPI are low affinity, mainly monoreactive autoantibodies directed to an epitope located on native beta2GPI, preserved along the species evolution.
Prolactin administration following hemorrhagic shock improves macrophage cytokine release capacity and decreases mortality from subsequent sepsis.
Authors: Zellweger R , Zhu X H , Wichmann M W , Ayala A , DeMaso C M , Chaudry I H 
Published: December 2022

Abstract
Although prolactin is reported to counteract the immunosuppressive effects of glucocorticoids, cyclosporine, and morphine, it remains unknown whether prolactin has any salutary effects on the depressed immune responses following severe hemorrhage. To study this, mice were bled to and maintained at a mean arterial pressure of 35 mm Hg for 60 min, then adequately resuscitated and divided into two groups. One group received saline vehicle, while the other group received prolactin (100 micro g/25 g body weight, s.c.) immediately before resuscitation. Two hours thereafter, peritoneal (pMphi) and splenic macrophages (sMphi) were harvested and assessed not only for their ability to release IL-1 and IL-6, but also for cytokine gene expression using semiquantitative reverse transcription and PCR. In an additional group, mice were subjected to sepsis by cecal ligation and puncture 3 days after hemorrhage. Hemorrhage markedly decreased the ability of pMphi and sMphi to release IL-1 and IL-6. This was, however, associated with increased mRNA expression for IL-1beta and IL-6 and increased serum corticosterone levels. Following prolactin treatment of hemorrhaged mice, IL-1beta and IL-6 mRNA levels as well as cytokine release capacity and blood corticosterone levels were comparable to the values in sham animals. Prolactin also improved the survival of animals subjected to sepsis after hemorrhage. Thus, the immunosuppression following hemorrhage appears to be mediated and modulated by hormones from the hypothalamic-pituitary-adrenal axis. Furthermore, prolactin represents a novel immunomodulating hormone for the treatment of immunodepression encountered after hemorrhagic shock and for decreasing the mortality from subsequent sepsis under those conditions.
Specific inhibition of T lymphocyte coactivation by triggering integrin beta 1 reveals convergence of beta 1, beta 2, and beta 7 signaling pathways.
Authors: Woodside D G , Teague T K , McIntyre B W 
Published: December 2022

Abstract
T cell coactivation is a dynamic process subject to integrin-dependent positive and negative regulation. Costimulation of human peripheral blood T cells by CD3 mAb OKT3 in conjunction with anti-alpha 4 has been shown to be down-regulated by the anti-beta 1.1 epitope-specific mAb 18D3. As expected, maximal costimulation induced by alpha 4-specific mAb L25 was inhibited (70%) by the addition of soluble mAb 18D3. Surprisingly, soluble mAb 18D3 inhibited maximal proliferation induced by the costimulatory alpha 4 beta 7-specific mAb ACT-1 by 40%, thus demonstrating that one integrin subfamily can regulate the activity of another. To determine whether mAb 18D3 could regulate more than alpha 4-associated integrin-mediated costimulation, non-alpha 4 integrins were tested. mAb 18D3 inhibited maximal proliferation induced by alpha 4-specific mAb 3D6, and an alpha 4-specific mAb 16. This clearly demonstrates that a variety of integrin costimulatory molecules (of the beta 1, beta 2, and beta 7 subfamilies) can be regulated negatively by mAb 18D3. To analyze the specificity of this negative regulation, other cell surface costimulatory molecules were tested for susceptibility to mAb 18D3. Although Abs specific for CD4, CD26, CD28, CD44, CD45RA, or CD45RO were sufficient to activate T cells when co-immobilized with anti-CD3 mAb, all were refractory to the inhibitory effects of mAb 18D3. Inhibition of T cell activation directly correlated with diminished IL-2 production. This suggests that mAb 18D3 selectively regulates integrin-dependent T cell activation by delivering a negative effect at some common point utilized by various integrin subfamilies.
Molecular mimicry between an immunodominant amino acid motif on the 47-kDa lipoprotein of Treponema pallidum (Tpp47) and multiple repeats of analogous sequences in fibronectin.
Authors: Baughn R E , Jiang A , Abraham R , Ottmers V , Musher D M 
Published: December 2022

Abstract
Molecular mimicry, resulting from structural similarities between self-determinants on host Ags and an organism's antigenic determinants (epitopes), can incite autoimmune events in certain bacterial and viral diseases. In the course of comprehensively mapping the 47-kDa lipoprotein (Tpp47) of Treponema pallidum subsp. pallidum using an overlapping synthetic peptide strategy, we identified a major immunoreactive epitope (411PGTEYT416) that exhibited considerable motif identity with multiple repeats of analogous linear sequences found in mammalian fibronectins. To further explore the importance of this motif as a probable instigator in the induction of polyspecific cross-reactive Abs, mimetic variants were synthesized for immunologic studies. Mimetics with ala (A) replacements in each amino acid position were used to determine which residues were critical for Ab binding. Animals immunized with two mimetics (PGTEYT or PGSEYT) coupled to tetanus toxoid exhibited: 1) modified responses when challenged with viable T. pallidum; and 2) classical Arthus reactions when challenged intradermally with either motif linked to a different carrier. The cross-reactive nature of the Ab responses to both mimetics was confirmed in a variety of ELISAs using mimetics, fibronectins, and collagens. Inhibition-ELISA studies with both fibronectin and an unrelated mimetic of the RGD motif suggest that intra- and intermolecular epitope spreading occurs following mimetic immunization and involves additional self-epitopes. These observations suggest that although molecular mimicry plays a pivotal role in initially triggering the anti-fibronectin and anti-collagen responses associated with disseminated syphilis, expansion of those autoimmune responses may be due to other self-epitopes once tolerance is abrogated.
CTL recognition of an altered peptide associated with asparagine bond rearrangement. Implications for immunity and vaccine design.
Authors: Chen W , Ede N J , Jackson D C , McCluskey J , Purcell A W 
Published: December 2022

Abstract
The extent to which peptides containing chemically and post-translationally modified amino acid side chains are recognized by primed CTL has not been clearly defined. We report on the CTL recognition of a MHC class I-restricted peptide containing a cyclized asparagine (succinimide) residue. This modification of the asparagine side chain is a common intermediate structure during deamidation, isomerization, and bond rearrangements of amide-containing amino acids and also occurs as a side reaction in peptide synthesis. The CTL specifically recognized the succinimide-containing peptide showing only weak cross-reactivity at high concentrations of the parent peptide containing unmodified asparagine. Similarly, CTL raised against the parent peptide did not recognize the succinimide derivative of this peptide. Naturally processed forms of these structures are likely to occur given the importance and frequency of deamidation both in vitro and in vivo. Moreover, since succinimide intermediates of deamidated peptides can occasionally be very stable, these peptides have the potential to act as altered self-Ags with significant implications for autoimmunity. In addition, unwanted and potentially hazardous specificities may be elicited when using synthetic peptides in subunit vaccines in which succinimide residues may form spontaneously during storage or chemical synthesis.