Biomedical subjects

A Nel

Publications and source records attributed to A Nel.

At least 19 recordsLinked to original sources

PubMed2000

Induction of heme oxygenase-1 expression in macrophages by diesel exhaust particle chemicals and quinones via the antioxidant-responsive element.

Diesel exhaust particles (DEP) contain organic chemicals that contribute to the adverse health effects of inhaled particulate matter. Because DEP induce oxidative stress in the lung and in macrophages, effective antioxidant defenses are required. One type of defense is through the expression of the antioxidant enzyme, heme oxygenase I (HO-1). HO-1 as well as phase II detoxifying enzymes are induced via antioxidant response elements (ARE) in their promoters of that gene. We show that a crude DEP total extract, aromatic and polar DEP fractions, a benzo(a)pyrene quinone, and a phenolic antioxidant induce HO-1 expression in RAW264.7 cells in an ARE-dependent manner. N-acetyl cysteine and the flavonoid, luteolin, inhibited HO-1 protein expression. We also demonstrate that the same stimuli induce HO-1 mRNA expression in parallel with the activation of the SX2 enhancer of that gene. Mutation of the ARE core, but not the overlapping AP-1 binding sequence, disrupted SX2 activation. Finally, we show that biological agents, such as oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, could also induce HO-1 expression via an ARE-dependent mechanism. Prior induction of HO-1 expression, using cobalt-protoporphyrin, protected RAW264.7 cells against DEP-induced toxicity. Taken together, these data show that HO-1 plays an important role in cytoprotection against redox-active DEP chemicals, including quinones.

Acetylcysteine↗

PubMed2000

Response differences between human CD4(+) and CD8(+) T-cells during CD28 costimulation: implications for immune cell-based therapies and studies related to the expansion of double-positive T-cells during aging.

Since CD28 costimulation is critical for T-cell activation, there is great interest in CD28 as a target for immuntherapeutic approaches. We show that stimulation of human CD4(+) and CD8(+) T-cells differs in their responsiveness to stimulation with anti-CD3/CD28-coated beads, as surrogate antigen-presenting cells. While the CD4(+) subset responded with sustained proliferation, CD8(+) T-cells grew for a limited period only and failed to produce IL-2 beyond the first few days in culture. This decrease is accompanied with an increased rate of apoptosis in CD8(+) T-cells despite Bcl-x(L) expression. The CD8(+) but not the CD4(+) subset developed a reversible double-positive phenotype during CD28 costimulation. This finding may have some bearing on the appearance of double-positive T-cells in human peripheral blood. This double-positive subset was shown to undergo a statistically significantly increase during aging in humans. Taken together, the above data have important implications for immunotherapy and immune senescence.

Adult↗

PubMed2000

In vivo nasal challenge with diesel exhaust particles enhances expression of the CC chemokines rantes, MIP-1alpha, and MCP-3 in humans.

Diesel exhaust particles (DEP) enhance allergic inflammation by increasing in vivo IgE and cytokine production in the human upper respiratory mucosa. CC chemokines have been shown to play an important role in inflammation. We examined whether DEP could alter the production of CC chemokines by cells residing in the human nasal mucosa. At both 6 and 24 h following intranasal DEP challenge, the levels of nasal RANTES, MIP-1alpha, and MCP-3 were significantly elevated compared to baseline. In contrast, DEP did not enhance levels of Eotaxin at any time, demonstrating that the action of DEP was not simply a global effect on all CC chemokines. Challenge with saline resulted in no significant change in expression of any chemokine at any time. Challenge with DEP also resulted in an increase in total cell counts in nasal lavage fluids. Increases in lymphocyte, monocyte/macrophage, and neutrophil cells were observed but there was no change in eosinophil cell numbers. In contrast, there was a significant enhancement of ECP protein levels in washes performed 6 to 24 h after DEP challenge. Elevated specific nasal chemokine expression following exposure to DEP likely participates in the inflammation, cellular infiltration, and increase in IgE observed in the absence of allergen.

Adult↗

PubMed1999

Inflammatory cytokines synergize with the HIV-1 Tat protein to promote angiogenesis and Kaposi's sarcoma via induction of basic fibroblast growth factor and the alpha v beta 3 integrin.

The Tat protein of HIV-1, a transactivator of viral gene expression, is released by acutely infected T cells and, in this form, exerts angiogenic activities. These have linked the protein to the pathogenesis of Kaposi's sarcoma (KS), a vascular tumor frequent and aggressive in HIV-1-infected individuals (AIDS-KS). In this study, we show that a combination of the same inflammatory cytokines increased in KS lesions, namely IL-1 beta, TNF-alpha, and IFN-gamma, synergizes with Tat to promote in nude mice the development of angioproliferative KS-like lesions that are not observed with each factor alone. Inflammatory cytokines induce the tissue expression of both basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), two angiogenic molecules highly produced in primary KS lesions. However, bFGF, but not VEGF, synergizes with Tat in vivo and induces endothelial cells to migrate, to adhere, and to grow in response to Tat in vitro. Tat angiogenic effects correlate with the expression of the alpha v beta 3 integrin that is induced by bFGF and binds the arginine-glycine-aspartic acid (RGD) region of Tat. In contrast, no correlation is observed with the expression of alpha v beta 5, which is promoted by VEGF and binds Tat basic region. Finally, KS lesion formation induced by bFGF and Tat in nude mice is blocked by antagonists of RGD-binding integrins. Because alpha v beta 3 is an RGD-binding integrin that is highly expressed in primary KS lesions, where it colocalizes with extracellular Tat on vessels and spindle cells, these results suggest that alpha v beta 3 competitors may represent a new strategy for the treatment of AIDS-KS.

Animals↗

PubMed1998

Macrophage activation by polycyclic aromatic hydrocarbons: evidence for the involvement of stress-activated protein kinases, activator protein-1, and antioxidant response elements.

Polycyclic aromatic hydrocarbons (PAH) contained in fossil fuel combustion particles enhance the allergic response to common environmental Ags. A key question is: what are molecular pathways in the immune system by which PAH and conversion products drive allergic inflammation? Circumstantial evidence suggests that macrophages are involved in PAH-induced responses. We demonstrate that a representative PAH, beta-napthoflavone (BNF), and a representative quinone metabolite, tert-butylhydroxyquinone (tBHQ), induce Jun kinase and p38 mitogen-activated protein kinase activities in parallel with the generation of activator protein-1 (AP-1) mobility shift complexes in THP-1 and RAW264.7 macrophage cell lines. Activation of mitogen-activated protein kinases was dependent on generation of oxidative stress, and could be inhibited by N-acetylcysteine. Another genetic response pathway linked to PAH is the antioxidant response element (ARE), which regulates expression of detoxifying enzymes. BNF and tBHQ activated a human ARE (hARE) reporter gene in RAW264.7 cells. Interestingly, bacterial lipopolysaccharide also induced hARE/chloramphenicol acetyltransferase activity. While the hARE core, GTGACTCAGC, contains a consensus AP-1 sequence (underlined), AP-1 was not required for hARE activation. This suggests that PAH and their conversion products operate via ARE-specific transcription factors in the immune system. BNF and tBHQ did, however, induce AP-1 binding to the hARE, while constitutively active Jun kinase interfered in hARE/chloramphenicol acetyltransferase activation. This suggests that AP-1 proteins negatively regulate the hARE. These data establish important activation pathways for PAH in the immune system and provide us with targets to modulate the effect of environmental pollutants on allergic inflammation.

Animals↗

PubMed1998

The c-Jun N-terminal kinase cascade plays a role in stress-induced apoptosis in Jurkat cells by up-regulating Fas ligand expression.

T lymphocytes undergo apoptosis in response to cellular stress, including UV exposure and gamma irradiation. However, the mechanism by which stress stimuli induce apoptosis is not well understood. While stress stimuli induce the activation of the c-Jun N-terminal kinase (JNK) pathway, it is not clear whether the JNK cascade is activated as a result of cell death or whether the cascade participates in inducing apoptosis. Using a Jurkat T cell line transfected with dominant active (DA)-mitogen-activated protein kinase kinase kinase (MEKK1) in a tetracycline-regulated expression system, we found that expression of DA-MEKK1 results in the apoptosis of Jurkat cells in parallel with prolonged JNK activation. Moreover, DA-MEKK1 induced Fas ligand (FasL) cell surface and mRNA expression, as well as FasL promoter activation. Interference with Fas/FasL interaction prevented DA-MEKK1-mediated apoptosis. In comparing the effect of different stress stimuli to DA-MEKK1, we found that UV, gamma irradiation, and anisomycin prolonged JNK activation in parallel with FasL expression and onset of cell death. In addition, these stimuli also enhance cell surface expression of FasL. Interference with Fas/FasL interactions inhibited anisomycin but not UV- or gamma irradiation-induced apoptosis. Our data show that while the JNK pathway contributes to stress-induced apoptosis in T lymphocytes by regulating FasL expression, not all stress stimuli use the same cell death pathway.

Apoptosis↗

PubMed1998

Latex antigens: identification and use in clinical and experimental studies, including crossreactivity with food and pollen allergens.

LEARNING OBJECTIVES: The purpose of this review is to introduce the reader to the range of latex allergens that have been identified by polypeptide sequencing. This knowledge is important for the assessment of clinical latex hypersensitivity, including crossreactivity with food and aeroallergens. DATA SOURCES: Medline search and relevant publications and reviews from the English medical literature since 1989. RESULTS: Of the more than 150 polypeptides in natural latex rubber, 35 or more can act as allergens and are recognized by IgE antibodies in the sera of latex-sensitive subjects. Complete or partial amino acid sequence data have now been obtained for 20 or more allergens, and have facilitated cloning of genes and development of allergen-specific antibodies. In latex-sensitive adults, hevein (Hev b6), rubber elongation factor (Hev b1) and Hev b5 are reported as major allergens, while in children with spina bifida, latex particle proteins are important allergens. Although incomplete, the data for finished latex products indicate that the number as well as diversity of latex antigens are limited compared with the allergen profile of natural rubber latex. Latex allergen sequence data allows epitope mapping, which establishes the molecular basis for understanding crossreactivity between latex, food, and aeroallergens. CONCLUSION: The identification of latex allergens is paving the way for studying the molecular basis of immunoreactivity to these proteins, including crossreactivity with food and other allergens. The development of reagents to detect and measure antigen-specific responses will increase diagnostic specificity of allergic reactions to latex products.

Allergens↗

PubMed1998

Stress-induced Fas ligand expression in T cells is mediated through a MEK kinase 1-regulated response element in the Fas ligand promoter.

T lymphocytes undergo apoptosis in response to a variety of stimuli, including exposure to UV radiation and gamma-irradiation. While the mechanism by which stress stimuli induce apoptosis is not well understood, we have previously shown that the induction of Fas ligand (FasL) gene expression by environmental stress stimuli is dependent on c-Jun N-terminal kinase (JNK) activation. Using inducible dominant-active (DA) JNK kinase kinase (MEKK1) expression in Jurkat cells, we map a specific MEKK1-regulated response element to positions -338 to -316 of the Fas ligand (FasL) promoter. Mutation of that response element abrogated MEKK1-mediated FasL promoter activation and interfered in stress-induced activation of that promoter. Using electrophoretic mobility shift assays, we demonstrate that activator protein 1 (AP-1) binding proteins, namely, activating transcription factor 2 (ATF2) and c-Jun, bind to the MEKK1 response element. Transient transfection of interfering c-Jun and ATF2 mutants, which lack the consensus JNK phosphorylation sites, abrogated the transcriptional activation of the FasL promoter, demonstrating the involvement of these transcription factors in the regulation of the FasL promoter. Taken together, our data indicate that MEKK1 and transcription factors regulated by the JNK pathway play a role in committing lymphocytes to undergo apoptosis by inducing FasL expression via a novel response element in the promoter of that gene.

Base Sequence↗

PubMed1996

[Dimensions of leadership practice by nursing service managers].

Leadership development is an important component of the nursing service manager's personal and professional development. Competent leadership is required to lead the nursing service in the right direction within the context of dynamic political and social changes. Various internal and external environmental variables have a significant influence on leadership behaviour and practice. The purpose with this study is to explore and describe the characteristics or dimensions of leadership excellence by the nursing service manager. An exploratory and descriptive research design was followed and data collection was done by means of focus group interviews. The results do not show a significant difference between the knowledge already generated by research, or described in the literature, but is utilised as the basis of leadership development of nursing service managers. A leadership development programme for nursing service managers, based on the results of this study, is recommended.

Focus Groups↗

PubMed1995

The membrane immunoglobulin receptor utilizes a Shc/Grb2/hSOS complex for activation of the mitogen-activated protein kinase cascade in a B-cell line.

Ligation of membrane immunoglobulin M (mIgM) receptor in the Ramos B-cell line induced tyrosine phosphorylation of several intracellular substrates, including the adaptor protein. Shc. Phosphorylated Shc could be seen to associate with Grb2 in a complex which included hSOS. Inasmuch as hSOS is involved in p21ras activation, we also demonstrated that mIgM ligation activated a Ras-dependent kinase cascade in which sequential activation of Raf-1 and MEK-1 culminates in the activation of p42 mitogen-activated protein (MAP) kinase (ERK-2). The tumour promoter and protein kinase C agonist, phorbol 12-myristate 13-acetate (PMA), also activated Raf-1, MEK-1, and MAP kinase in Ramos cells, but did not induce tyrosine phosphorylation of Shc or Shc/Grb2 association. Okadaic acid, another tumour promoter and serine/threonine phosphatase inhibitor, activated p42 MAP kinase without activating Raf-1 or MEK-1, suggesting the existence of a serine/threonine phosphatase which directly regulates MAP kinase activity.

Adaptor Proteins, Signal Transducing↗

PubMed1995

Definition of a lamina propria T cell responsive state. Enhanced cytokine responsiveness of T cells stimulated through the CD2 pathway.

This study was designed to compare cytokine release in lamina propria lymphocytes (LPLs) and PBLs activated by Abs against CD3, CD2, and CD28. LPL T cells were significantly more responsive to CD2 ligation than PBL, as determined by release of IFN-gamma, IL-2, IL-4, and TNF-alpha. Moreover, CD28 co-ligation in LPLs exaggerated CD2 > CD3 dominance in cytokine induction. PHA-activated PBLs expressed more CD2 receptors than freshly isolated LPLs, but were less responsive to activation through CD2, indicating that postreceptor pathways in LPL may be adapted specifically to facilitate CD2-mediated cytokine secretion. Antiphosphotyrosine (APT) immunoblotting revealed inducible substrate phosphorylation during CD2, but not CD3, ligation in whole LPLs, as well as LPL-derived T cell lines. PBLs cocultured with an irradiated B cell line, Daudi, and IL-2 for 5 days attained a CD2-dominant cytokine-secretion pattern with identical tyrosine phosphorylation profiles as freshly isolated LPL or LPL T cell lines. PHA-activated PBLs did not produce these tyrosine phosphorylation profiles. This suggests that B lymphocytes in the lamina propria may contribute to a T cell differentiation process in which CD2, possibly by potentiation of its postreceptor pathway, becomes a prominent receptor for induction of cytokine secretion.

Animals↗

PubMed1995

Interleukin 4 activates a signal transducer and activator of transcription (Stat) protein which interacts with an interferon-gamma activation site-like sequence upstream of the I epsilon exon in a human B cell line. Evidence for the involvement of Janus kinase 3 and interleukin-4 Stat.

Germ line C transcripts can be induced by IL-4 in the human B cell line, BL-2. Utilizing a IFN-gamma activation site-like DNA sequence element located upstream of the I epsilon exon, we demonstrated by gel mobility shift assays that IL-4 induced a binding activity in the cytosol and nucleus of BL-2 cells. This factor was designated IL-4 NAF (IL-4-induced nuclear-activating factors) and was identified as a tyrosine phosphoprotein, which translocates from the cytosol to the nucleus upon IL-4 treatment. Because these are the characteristics of a signal transducer and activator of transcription (Stat) protein, we determined whether antibodies to Stat proteins will interfere with gel mobility shift and found that antibodies to IL-4 Stat, also known as Stat6, but not antibodies to other Stat proteins, interfere with the formation of the IL-4 NAF complex. Congruous with the involvement of a Stat protein, IL-4 induced robust Janus kinase 3 (JAK3) activity in BL-2 cells. Cotransfection of JAK3 with IL-4 Stat into COS-7 cells produced an intracellular activity which bound the same IFN-gamma activation site-like sequence and comigrated with IL-4 NAF in electrophoretic mobility shift assay. These results show that IL-4 NAF is IL-4 Stat, which is activated by JAK3 in response to IL-4 receptor engagement.

Animals↗

PubMed1994

The T-cell antigen receptor utilizes Lck, Raf-1, and MEK-1 for activating mitogen-activated protein kinase. Evidence for the existence of a second protein kinase C-dependent pathway in an Lck-negative Jurkat cell mutant.

T-cell antigen receptor (TCR) ligation of an Lck-deficient Jurkat mutant, J.CaM1, with anti-CD3 or anti-TCR beta monoclonal antibodies failed to induce tyrosine phosphorylation and activation of p42MAPK. The same stimuli activated mitogen-activated protein (MAP) kinase in J.CaM1 cells transfected with Lck, demonstrating that Lck plays a critical role in MAP kinase activation. Utilizing immunocomplex kinase assays, we demonstrated that TCR/CD3 ligation activated a MAP kinase kinase kinase (Raf-1) as well as a MAP kinase kinase (MEK-1) in Jurkat but not in J.CaM1 cells. It was possible, however, to activate Raf-1, MEK-1, and p42MAPK in J.CaM1 cells during treatment with the phorbol ester phorbol 12-myristate 13-acetate, which activates protein kinase C (PKC). This demonstrates the presence of a PKC-dependent pathway which functions independently from Lck in MAP kinase activation. Stimulation of Jurkat cells with either anti-TCR beta or anti-CD3 monoclonal antibody failed to induce substantial tyrosine phosphorylation of Shc proteins or their association with Grb2 which forms a complex with the guanine nucleotide exchange factor hSOS. However, the same stimuli induced tyrosine phosphorylation of another putative guanine nucleotide exchange factor, p95Vav, in Jurkat but not J.CaM1 cells. Moreover, Lck was reversibly co-immunoprecipitated with p95Vav, and the stoichiometry of binding increased in anti-CD3-treated Jurkat cells. Phorbol 12-myristate 13-acetate did not induce tyrosine phosphorylation of p95Vav. These data show that the TCR activates MAP kinase by way of a signaling cascade, which depends upon Lck, and may be mediated by downstream events involving PKC or p95Vav which act on Raf-1 and MEK-1.

Cell Line↗

PubMed1993

Intestinal intraepithelial lymphocytes are activated and cytolytic but do not proliferate as well as other T cells in response to mitogenic signals.

Compared with T lymphocytes from other organs, intestinal intraepithelial lymphocytes (IEL) proliferate weakly in response to CD3/TCR ligation, and they do not respond at all to treatment with other mitogenic stimuli. These signals also failed to induce expression of the IL-2R alpha-chain on the surface of most IEL. IEL from germ-free mice, from V gamma 1.1-transgenic mice, and from beta 2-microglobulin-deficient mice also gave a weak proliferative response. Therefore, the low proliferative response is not linked to the level of exposure to gut bacterial flora, the V gamma region expressed by the TCR-gamma delta + IEL, or the presence of class I molecules that may be recognized by CD8+ IEL. The relatively small amount of proliferation in response to TCR signaling, therefore, is not likely to be the result of induction of anergy caused by previous contact with Ag. In contrast, ligation of the CD3/TCR complex could elicit a rapid cytotoxic response and serine esterase release by IEL. The unusual functional capabilities and the activation state of IEL are independent of the TCR isotype expressed by these cells. Freshly isolated IEL have a high intracellular microtubule-associated protein kinase-2 (MAP-2K) activity level, further suggesting that these cells are activated despite their weak proliferative response. Consistent with this, MAP-2K is tyrosine-phosphorylated in both untreated and PMA-treated IEL. In contrast, MAP-2K activation and tyrosine phosphorylation occur in other T cells only when they are activated by PMA or other treatments. MAP-2K activity also is elevated in IEL from germ-free mice, demonstrating that activation does not depend on normal levels of exposure to bacterial flora. The activation of protein kinases such as MAP-2K could reflect the differentiation state of IEL or Ag receptor stimulation of some of these cells by epithelial cells in the preparation.

Animals↗

PubMed1991

Nerve growth factor stimulates the tyrosine phosphorylation of MAP2 kinase in PC12 cells.

NGF treatment of PC12 cells results in the rapid activation of MAP2 kinase. We report here that the induction of enzyme activity was correlated with the phosphorylation of MAP2 kinase, detected by metabolic labeling of the enzyme and with anti-phosphotyrosine antibodies. NGF stimulated the phosphorylation of MAP2 kinase on tyrosine, as well as serine and threonine residues. Western blot analysis using a polyclonal anti-phosphotyrosine antibody demonstrated that the tyrosine phosphorylation of MAP2 kinase was maximal within 2 min following NGF exposure and preceded the induction of MAP2 kinase activity. The NGF-stimulated tyrosine phosphorylation of an identified substrate provides direct evidence for the participation of a tyrosine kinase in the mechanism of action of NGF.

Adrenal Gland Neoplasms↗

PubMed1990

HIV inhibits the early steps of lymphocyte activation, including initiation of inositol phospholipid metabolism.

Mechanisms accounting for HIV-associated suppression of lymphocyte proliferation were investigated. In previous work we demonstrated that purified and inactivated HIV-suppressed lymphoid cell proliferation. In this report we used an inactivated preparation of HIV obtained from infected CEM cells grown in serum free media and demonstrated that this HIV-associated suppression acted in the early steps of activation to inhibit the incorporation of radiolabeled phosphorus into phosphatidylinositol 4,5-bisphosphate and phosphatidic acid. Initially we showed that both purified CD4 and CD8 T lymphocyte subsets were affected and HIV-associated inhibition did not require the CD4 molecule. Impaired lymphocyte blastogenesis (decreased size and granularity and decreased expression of receptors to IL-2 and transferrin) in response to PHA indicated an effect of inactivated HIV on the early steps of activation. This was confirmed by time studies where 1) a 2 min HIV-pretreatment followed by washing before stimulation was sufficient to inhibit PHA induced proliferation of normal lymphocytes, and 2) addition of HIV to PHA prestimulated lymphocytes failed to inhibit proliferation, e.g., there was no effect on preactivated lymphocytes. HIV was mainly inhibitory of lymphocyte proliferation induced by PHA or mAb to the CD3 receptor. In contrast to the effect on the CD3/TiR, responses via the CD2 receptor were not suppressed, e.g., stimulation with the monoclonal antibodies T11(2) + T11(3). Inasmuch as responses by direct A23187 + PMA stimulation of intracellular pathways were also inhibited, it appears that the HIV-induced defect was not (or not only) membrane receptor mediated. The earliest (min) measurable event after stimulation was the initial increase in intracellular Ca2+ which was unaffected by HIV pretreatment. The next measurable event (min to h) of stimulation is a sustained increase in inositol phospholipid turnover. Pretreatment of mononuclear cells with inactivated HIV resulted in a decreased inositol phospholipid turnover as judged from decreased 32P incorporation into phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate. This led to decreased generation of DAG as reflected in the reduced radiolabeling of its metabolite PA. Reduced availability of DAG presumably interferes with pkC activation and leads to decreased expression of receptors for IL-2 and transferrin and impaired proliferation.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1989

Complexing of the CD-3 subunit by a monoclonal antibody activates a microtubule-associated protein 2 (MAP-2) serine kinase in Jurkat cells.

Treatment of Jurkat T-cells with anti-CD-3 monoclonal antibodies resulted in the rapid and transient activation of a serine kinase which utilized the microtubule-associated protein, MAP-2, as a substrate in vitro. The kinase was also activated on treatment of Jurkat cells with phytohaemagglutinin, but with a different time course. The activation of the MAP-2 kinase by anti-CD-3 antibodies was dose-dependent, with maximal activity observed at concentrations of greater than 500 ng/ml. Normal human E-rosette-positive T-cells also exhibited induction of MAP-2 kinase activity during anti-CD-3 treatment. The enzyme was optimally active in the presence of 2 mM-Mn2+; lower levels of activity were observed with Mg2+, even at concentrations up to 20 mM. The kinase was partially purified by passage over DE-52 Sephacel with the activity eluting as a single peak at 0.25 M-NaCl. The molecular mass was estimated to be 45 kDa by gel filtration. The activation of the MAP-2 kinase was probably due to phosphorylation of this enzyme as treatment with alkaline phosphatase diminished its activity. These data demonstrate that the stimulation of T-cells through the CD-3 complex results in the activation of a novel serine kinase which may be critically involved in signal transduction in these cells.

Antibodies, Monoclonal↗

PubMed1986

Inhibitory effect of an antibody against alpha 1-acid glycoprotein (alpha 1-AGP) on autologous mixed lymphocyte reaction and anti-T3 T-lymphocyte activation.

The action of an anti-alpha 1-AGP antibody on AMLR, anti-T3 and PHA T-lymphocyte proliferative response was evaluated. We observed a strong dose-dependent inhibition on T-lymphocyte proliferative responsiveness to autologous non-T cells and to anti-T3 stimulus, whereas PHA activation was unaffected. A lower degree of inhibition of the proliferative response was also observed on pretreating both T and non-T cells with the antibody; the addition of anti-alpha 1-AGP in the culture containing cells pretreated with the antibody showed a further inhibition of thymidine incorporation. The data suggest a direct influence of the antibody on membrane alpha 1-AGP and support a positive role of this glycoprotein (distinct from Ia and T3 antigens) on both anti-T3 and autologous non-T cell T-lymphocyte responsiveness, thus indicating the involvement of alpha 1-AGP in the T3-Ti antigen-specific pathway of T-cell activation.

Adult↗