bluuebunny/crossref_metadata_2025_split huggingface dataset:
LTB4 induced activation signals and responses in neutrophils are short-lived compared to formylpeptide.
Authors: Omann G M , Traynor A E , Harris A L , Sklar L A 
Published: December 2022

Abstract
Leukotriene B4 (LTB4) was shown to be a potent stimulator of neutrophil actin polymerization as detected by right-angle light scatter and rhodamine-phalloidin staining of F-actin. When we compared the kinetics of this neutrophil cytoskeletal response to the chemoattractants formylpeptide and LTB4, we observed that the response to LTB4 was markedly shorter-lived. To understand the basis of this result, we re-examined the kinetics of superoxide generation, elastase release, intracellular calcium elevation, and phosphoinositide metabolism in neutrophils stimulated with LTB4 and N-formylhexapeptide. LTB4 was relatively inefficient in producing superoxide and in releasing elastase. Although both responses were initiated with similar rapidity, they turned off sooner with LTB4 as compared with N-formylhexapeptide stimulation. Intracellular calcium elevation, a signal that is necessary for superoxide generation and degranulation, was of similar magnitude but of shorter duration in response to LTB4 as compared with the N-formylhexapeptide. The LTB4-induced rise of phosphatidic acid also was not sustained as long as the N-formylhexapeptide-induced increase. Prior exposure of neutrophils to LTB4 did not inhibit subsequent stimulation of superoxide generation by N-formylhexapeptide. Thus, the inability of LTB4 to stimulate superoxide generation was not due to LTB4-induced global inhibitory signals. The deficiency in LTB4-induced superoxide and elastase responses may be related to short-lived LTB4-induced activation signals and/or the number of receptors contributing to these responses.
Modulation of the biological activity of bacterial endotoxin by incorporation into liposomes.
Authors: Dijkstra J , Mellors J W , Ryan J L , Szoka F C 
Published: December 2022

Abstract
In an attempt to define the mechanism by which endotoxin induces its biological activity, we studied the effect of the incorporation of lipopolysaccharide and lipid A into phospholipid vesicles (liposomes) on the stimulation of the macrophage cell-line RAW 264.7 and on the coagulation of Limulus amoebocyte lysate. The incorporation of Salmonella minnesota smooth-and rough (Re) lipopolysaccharide or primarily monophosphoryl lipid A into multilamellar and small unilamellar vesicles consisting of phosphatidylcholine, phosphatidylserine and cholesterol (molar ratio 4:1:4) reduced the interleukin 1 inducing potency of these substances about 1000-fold. When corrected for the actual uptake of radiolabeled free and liposome-incorporated lipopolysaccharide by the cells, this difference amounted to 100- to 1000-fold. In addition, liposome-associated Re-lipopolysaccharide was about 1000-fold less potent in stimulating the Fc-receptor mediated uptake of IgG-coated sheep erythrocytes by the cells. The ability of lipopolysaccharide and lipid A to coagulate the Limulus amoebocyte lysate appeared to be at least 100-fold decreased upon incorporation into phospholipid vesicles. Control experiments demonstrated that liposomes prepared without lipopolysaccharide did not reduce the studied activities of free lipopolysaccharide. In conclusion, the incorporation of lipopolysaccharide into the liposomal membrane probably prevents the interaction of the hydrophobic portion of the lipid A component of lipopolysaccharide with the plasma-membrane structures involved in the activation of macrophages and with the proteins of the Limulus amoebocyte lysate. This indicates that the direct interaction of the lipid A moiety of lipopolysaccharide with the macrophage plasma-membrane is required to optimally trigger the studied responses.
Human T cell gamma chain joining regions and T cell development.
Authors: Quertermous T , Strauss W M , Van Dongen J J , Seidman J G 
Published: December 2022

Abstract
We have cloned and sequenced two homologous J regions of the T cell gamma gene and localized one 5' of each constant region. They have been numbered J gamma 1.1 and J gamma 2.1; other J regions have been renamed in a similar manner. Southern blot analysis suggests that there is comparatively more rearrangement to these J regions in thymocytes than peripheral blood T cells. We propose that either there is gamma-chain gene rearrangement first to J gamma 1.1 or 2.1 and then to J gamma 1.3 or 2.3, or there is selected cell death of thymic T cells bearing a J gamma 1.1 or 2.1 rearrangement.
Cytochalasin induces an increase in cytosolic free calcium in murine B lymphocytes.
Authors: Baeker T R , Simons E R , Rothstein T L 
Published: December 2022

Abstract
Cytochalasin promotes the progression of anti-immunoglobulin-treated B lymphocytes to S phase. However, the intracellular events induced by cytochalasin which may mediate signaling for progression have not been elucidated. In this study, the effect of cytochalasin on the level of intracellular free calcium in murine splenic B lymphocytes was assessed by using the fluorescent calcium indicator Indo-1. Cytochalasins A, B, D, and E induced a rapid and sustained elevation of intracellular free calcium. The calcium response to cytochalasin derived largely from the influx of extracellular calcium, although a small, transient elevation in intracellular calcium persisted when the suspension medium was made calcium-free with EGTA, implicating an intracellular source for a portion of the calcium response. Single cell fluorescence studies revealed that cytochalasin elicited a calcium response in most splenic B cells in suspension, indicating that this phenomenon is not restricted to a subpopulation of responding B cells. Phorbol esters inhibited the B cell calcium response to cytochalasin, and an established response to cytochalasin was rapidly and completely reversed by subsequently administered phorbol ester. T cells that lack the cytochalasin pathway showed a markedly diminished calcium response that was only apparent at higher cytochalasin concentration. However, B cells from xid-defective [CBA/N X DBA/2]F1 males, which fail to respond to anti-immunoglobulin plus cytochalasin, showed a calcium response to cytochalasin similar to that of phenotypically normal F1 females. These data, along with the finding that the rise in intracellular calcium occurred in naive B cells as well as B cells previously treated with anti-immunoglobulin, suggest that there is no clear association between the calcium response induced by cytochalasin and the ability of cytochalasin to stimulate progression to S phase. However, this effect of cytochalasin may suggest a connection between actin filaments and calcium influx in B cells.
Cytostatic and cytotoxic activity of tumor necrosis factor on human cancer cells.
Authors: Ruggiero V , Latham K , Baglioni C 
Published: December 2022

Abstract
The cytostatic and cytotoxic activity of human recombinant tumor necrosis factor (rTNF) was assayed on different tumor cell lines. Human BT-20 breast and ME-180 cervix cancer cells were growth-inhibited by rTNF, whereas two other cell lines were not significantly inhibited. However, when protein synthesis was inhibited by cycloheximide, rTNF was cytotoxic for these cells but not for BT-20 cells. This finding suggested that different mechanisms are responsible for the cytostatic and cytotoxic activity of rTNF. The sensitivity of different cell lines to rTNF could not be correlated with a high number or affinity of rTNF receptors. Occupancy of only a few receptors was sufficient for rTNA cytotoxicity, but an increase in receptor number after treatment with interferon-gamma, or a decrease after pretreatment with cycloheximide, correspondingly enhanced or depressed the cytotoxicity of rTNF. It seemed possible that some cells could be protected from this effect of rTNF by synthesizing "protective" proteins. While searching for such proteins, we observed that rTNF induced the synthesis of two polypeptides in SK-MEL-109 melanoma cells, but not in other cancer cells. Actinomycin D added with rTNF abolished synthesis of these polypeptides, suggesting that rTNF induced transcription of the corresponding mRNAs. Surprisingly, rTNF stimulated growth of SK-MEL-109 cells cultured in medium with low serum.
Expression of a 120,000 dalton protein during tumoricidal activation in murine peritoneal macrophages.
Authors: Johnston P A , Somers S D , Hamilton T A 
Published: December 2022

Abstract
Modulation of protein expression during interferon-gamma (IFN-gamma)-lipopolysaccharide (LPS)-mediated macrophage tumoricidal activation has been examined by metabolic radiolabeling of various murine peritoneal macrophage populations with [35S]methionine followed by SDS-PAGE analysis. Although both IFN-gamma and LPS are capable of stimulating the expression of several proteins when used independently, combined treatment induced the enhanced or de novo expression of a 120,000 dalton polypeptide. The expression of this protein was synergistically regulated by both IFN-gamma and LPS in a manner strongly reminiscent of the functional synergism that these two agents exhibit with respect to induction of tumoricidal activity. p120 expression could be seen first at approximately 3 hr after the addition of both agents, reached optimal expression by 6 hr, and maintained elevated synthesis for up to 24 hr. This time course corresponds closely to that seen for the acquisition of tumoricidal competence. Macrophages elicited in the primed state of activity in vivo with methyl vinyl ether co-polymer II (MVE-II) did not express p120, but could be induced to do so when treated with low doses of LPS. Under similar conditions, MVE-II-elicited cells also acquire tumoricidal activity. Macrophages obtained from mice chronically infected with bacillus Calmette-Guerin constitutively expressed both p120 and cytolytic activity. If such macrophages were cultured for 24 hr, the expression of both events decayed and was lost, but could be restored by treatment with low doses of LPS. Thus the data support a strong correlation between the expression by macrophages of a novel 120,000 dalton protein and the expression of tumor cytotoxicity.
Cationization of protein antigens. II. Alteration of regulatory properties.
Authors: Muckerheide A , Domen P L , Michael J G 
Published: December 2022

Abstract
Immunoregulatory effects of cationized bovine serum albumin (cBSA) and native bovine serum albumin (nBSA) have been investigated. Intravenous administration of nBSA to BDF1 mice substantially suppressed the antibody response to subsequent immunization with either nBSA or cBSA, whereas pretreatment with cBSA by the same route significantly enhanced the responses to both antigens. The functional properties of BSA-specific T and B cells from mice immunized with cBSA or nBSA were examined in reconstitution experiments in which splenic T populations together with B cells were transferred into irradiated syngeneic recipients. Transfer of splenic T cells from mice primed with nBSA caused profound suppression of the response to subsequent immunization with nBSA or cBSA, whereas transfer of either B or T cells from cBSA treated mice produced an enhanced response to both antigens. C57BL/6 mice, which are considered to be low responders to BSA, produced a significant antibody response to BSA when immunized with cBSA. In contrast, immunization with nBSA did not produce measureable amounts of antibody in mice of this strain. Our data clearly demonstrate that cationized BSA exhibits unique immunogenic properties due to alterations in the self-regulation of the immune response.
T cell priming in vivo: a major role for B cells in presenting antigen to T cells in lymph nodes.
Authors: Ron Y , Sprent J 
Published: December 2022

Abstract
Previous studies have shown that lymph node (LN) T cells from mice given repeated injections of anti-mu antisera from birth (mu sm) fail to mount secondary T proliferative responses to antigen in vitro after s.c. priming in vivo. This finding raised the possibility that priming of T cells in LN depends on the presence of B cells, Ig+ B lymphocytes being absent in mu sm. In support of this idea, the present paper shows that the priming defect in LN of mu sm can be largely overcome by injecting B cell populations s.c. 1 day before s.c. priming with antigen. Restoration of LN priming was observed with s.c. injection of highly purified populations of small B cells but not with heat-killed or lightly irradiated B cells. Homing studies indicated that approximately 10% of s.c.-injected B cells reached the draining LN. In other studies, irradiated mice injected i.v. with purified T cells manifested poor priming in LN after s.c. injection of antigen. It was reasoned that the LN priming defect in this situation reflected the lack of B cells in irradiated mice, B cells being highly radiosensitive. In support of this notion, it was found that s.c. injection of B cells into irradiated recipients of T cells led to high priming of T cells in LN after s.c. injection of antigen. Although T cells exposed to antigen in B-depleted LN of mu sm and irradiated mice gave negligible T proliferative responses in vitro, low but significant levels of primed T helper function were detected in a sensitive T helper assay in vivo. In light of this finding, our working hypothesis is that the initial induction of T cells to antigen in LN is controlled by resident dendritic cells (or other non-B antigen-presenting cells), the main role of B cells being to control the clonal expansion of activated T cells.
Interferon blocks interleukin 1-induced prostaglandin release from human peripheral monocytes.
Authors: Browning J L , Ribolini A 
Published: December 2022

Abstract
We have studied the short-term effects of interleukin 1, lipopolysaccharide, and interferon on prostaglandin release from freshly isolated human peripheral monocytes. When the cells were pretreated for 8 to 9 hr with either E. coli lipopolysaccharide or recombinant interleukin 1 (beta), prostaglandin release increased. Inclusion of recombinant IFN-alpha or IFN-gamma during the pretreatment phase blocked subsequent prostaglandin release. Interferons were effective at concentrations in the range of 1 to 10 antiviral units/ml, and the inhibition was manifested within several hours after exposure to the lymphokine. Similar trends were observed by measuring thromboxane release. These data suggest antagonistic roles for interleukin 1 and interferon in the regulation of eicosanoid release from monocytes.
Cell matrix adhesion-related proteins VLA-1 and VLA-2: regulation of expression on T cells.
Authors: Hemler M E , Jacobson J G 
Published: December 2022

Abstract
The mitogens phytohemagglutinin (PHA) and concanavalin A inhibited the appearance of the very late activation antigen (VLA)-1, but did not inhibit VLA-2 expression on cultured activated T cells. In contrast to diminished VLA-1 expression, mitogen treatment caused increased cell surface expression of other activation antigens such as T10, HLA-DR, interleukin 2 (IL 2) receptor, and 4F2, and greater cell proliferation. Conversely, when T cells were not repetitively restimulated with mitogen, these less proliferative "postactivated" T cells had elevated VLA-1 expression. The diminished expression of VLA-1 caused by PHA was reversible since subsequent removal of mitogen was associated with increased VLA-1, paralleled by a decrease in interleukin 2 receptor levels. In addition to preventing or delaying the initial appearance of VLA-1, PHA stimulation also was somewhat effective in causing the disappearance of VLA-1 already present, especially on recently established cultures. However, cultures that had either never seen PHA, not seen PHA for several weeks, or been stimulated regularly with PHA, but were several months old, did not lose VLA-1 in response to PHA stimulation, suggesting that a state of insensitivity to PHA effects could be attained. Unlike PHA-stimulated T cells, T cells repetitively restimulated with alloantigen or the monoclonal antibody T3 did not show a marked absence of VLA-1 but rather showed an increased level of VLA-2 relative to VLA-1. Taken together, results of stimulation by either mitogen, alloantigen, or anti-T3 monoclonal antibody support the conclusion that T cell stimulation in general can cause a decreased VLA-1:VLA-2 ratio, whether by decreased VLA-1 or increased VLA-2. These shifts in VLA-1:VLA-2 ratios are probably not simply the result of shifts in the relative proportions of different subpopulations, because similar growth-related changes in this ratio were observed on the T cell line ANITA, which is a homogeneous population of cells. Because both VLA-1 and VLA-2 are differentially regulated on cultured, long term activated T cells depending on stage of activation and growth conditions, and are members of a family of at least five heterodimers that includes cell matrix adhesion molecules, we suggest that these studies will provide clues to novel aspects of T cell growth regulation, perhaps relating to T cell-matrix adhesion.
An hypothesis on the binding of an amphipathic, alpha helical sequence in Ii to the desetope of class II antigens.
Authors: Elliott W L , Stille C J , Thomas L J , Humphreys R E 
Published: December 2022

Abstract
When we investigated the hypothesis that amphipathic alpha helical peptides digested from foreign antigen bind to class II major histocompatability complex (MHC) molecules' binding site (desetope) for foreign antigen to be presented to T cell receptors, we found such an extended amphipathic helix in Ii. This amphipathic helix was hypothesized to bind Ii to class II MHC antigens until release in endosomes containing digested foreign antigen. Then these amphipathic Ii polypeptides might polymerize so as not to compete with foreign antigen for binding to class II MHC molecules. Various structural models were consistent with these views and led to the suggestion of specific forms of polymeric interaction.
Monoclonal antibodies to the human C3b/C4b receptor (CR1) enhance specific B cell differentiation.
Authors: Weiss L , Delfraissy J F , Vazquez A , Wallon C , Galanaud P , Kazatchkine M D 
Published: December 2022

Abstract
The addition of monoclonal antibodies against the human C3b/C4b receptor (CR1) to cultures of peripheral blood lymphocytes in the presence of suboptimal amounts of TNP bound to polyacrylamide beads enhanced by 150 to 400% the specific anti-TNP response, as measured by a plaque-forming cell assay on day 7. Anti-CR1 antibodies similarly enhanced the anti-fluorescein antibody response. Enhancement only occurred in cultures performed in the presence of the relevant antigen. No enhancing effect on the anti-TNP response was observed on addition to cultures of monoclonal antibodies directed against other surface antigens of B cells or an anti-T cell antibody of the same subclass as that of anti-CR1 antibodies. Anti-CR1 antibodies alone did not induce nonspecific B cell proliferation and did not provide B cells with a first signal for proliferation in the presence of a source of B cell growth factors. Anti-CR1 antibodies did not enhance the nonspecific proliferative response of B cells to growth factors derived from PHA-stimulated T cells, semi-purified BCGF 20 KD, BCGF 50 KD, or recombinant IL 2 in the presence of anti-mu. In this respect, the effect of anti-CR1 antibodies differs from that of anti-CR2 antibodies which interact with early stages of B cell activation. In contrast, anti-CR1 antibodies enhanced specific differentiation of antigen-activated B cells in the absence of T cells when soluble T cell factors were provided. Similar results were obtained by using either of two sources of differentiation factors, the MLA-144 supernatant or a 30 to 15 KD fraction from PHA-stimulated T cells. These results indicate that triggering of CR1 on B cells positively regulates the specific antibody response to low doses of antigen by enhancing B cell differentiation whether T cell help is provided by intact T cells or by T cell-derived differentiation factors.
Lymphokine synthesis is induced in human thymocytes by activation of the CD 2 (T11) pathway.
Authors: Reem G H , Carding S , Reinherz E L 
Published: December 2022

Abstract
This study shows that unfractionated thymocytes can be activated to proliferate in response to activation by the CD 2 pathway, to express interleukin 2 receptors, and to synthesize interleukin 2 and interferon-gamma. Less mature, T3- thymocytes, isolated by negative selection are activated to a lesser extent than are unfractionated thymocytes; activation by the CD 2 pathway, induces proliferation, the expression of the interleukin 2 gene and interferon-gamma synthesis. 12-O-Tetradecanoyl phorbol 13-acetate in combination with the anti-CD 2 antibodies T11(2) + T11(3) increases the response of both unfractionated and T3- thymocytes. In addition we demonstrate that tetradecanoyl phorbol acetate in combination with T11(3) can replace the requirement for T11(2) for thymocyte activation and induce the expression of T11(3).
Internalization and degradation of receptor-bound interferon-gamma by murine macrophages. Demonstration of receptor recycling.
Authors: Celada A , Schreiber R D 
Published: December 2022

Abstract
Although the interferon-gamma (IFN-gamma) receptor on murine and human mononuclear phagocytes has been defined and partially characterized, very little data exists which describes the ultimate fate of receptor-bound ligand. The current studies were specifically designed to define the metabolic processes which act on murine recombinant IFN-gamma following its interaction with murine macrophages at physiologic temperatures. Ligand internalization was demonstrated by comparing binding of [125I]IFN-gamma to macrophages at 4 degrees C and 37 degrees C. When binding was carried out at 4 degrees C, 96% of the cell-associated [125I]IFN-gamma remained accessible at the plasma membrane and could be stripped from the cell by exposure to pronase. In contrast, at 37 degrees C, only 35% of the cell-associated radioactivity was pronase strippable. Macrophages degraded [125I]IFN-gamma into trichloroacetic acid-soluble material at 37 degrees C at a constant rate of 7000 molecules/cell/hr over a 12-hr time period. The amount of IFN-gamma degraded correlated with the amount of IFN-gamma bound to the cell surface. The receptor was neither up- nor down-regulated by ligand or by other agents known to regulate macrophage functional activity such as IFN-alpha, IFN-beta, lipopolysaccharide, or phorbol myristate acetate. The constant uptake of IFN-gamma by macrophages was due to the presence of an intracellular receptor pool (62% of the total receptor number) and to a mechanism of receptor recycling. Evidence for the latter was obtained using lysosomotropic agents which blocked degradation but not binding and internalization of ligand and caused the intracellular accumulation of receptor. By comparing the relationship between receptor occupancy and biologic response induction, two activation mechanisms became apparent. Induction of certain functions, such as H2O2 secretion, appeared to require only a single round of receptor occupancy. However, induction of more complex functions such as nonspecific tumoricidal activity appeared to require three to four rounds of receptor occupancy. These results thus support the concept that IFN-gamma internalization and receptor recycling are essential in the induction of nonspecific tumoricidal activity by macrophages.