Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclosporin A (CsA) is an immunosuppressive agent that inhibits the synthesis of lymphokines by T lymphocytes at the level of transcription. A cytoplasmic protein, cyclophilin, is the most thoroughly studied CsA-binding protein, but its ubiquitous presence in cells of all types raises questions about its role in immunosuppression. In an attempt to ascertain the presence of a cell surface receptor, we synthesized two polyvalent macromolecular CsA derivatives, CsA-BBa-ovalbumin and CsA-BBa-aminodextran (CBD), from the product of the photochemical reaction of CsA and 4-benzoylbenzoic acid (CsA-BBa). (i) They inhibited the peptidylprolyl cis-trans isomerase activity of cyclophilin and the synthesis of interleukin 2 by phorbol ester-activated EL-4 cells. (ii) CBD also inhibited interleukin 2 secretion by Con A-activated T-cell-enriched mouse splenocytes. 4-Benzoylbenzoic acid (BBa)-aminodextran and aminodextran were inactive. (iii) Direct binding and competition studies with [3H]CsA indicated that CBD does not enter EL-4 cells (i.e., it acted at the surface). (iv) CBD caused agglutination of EL-4 cells, murine B and T lymphocytes, human thymocytes, and two T-cell hybridomas. Agglutination was inhibited by a monoclonal antibody to CsA and by CsA and CsA-BBa, but not by BBa. No agglutination was seen with BBa-aminodextran or aminodextran. HeLa cells, Vero (monkey kidney) cells, a mouse plasmacytoma, COS cells, and a poorly differentiated B-cell lymphoma were not agglutinated. (v) EL-4 cells failed to be agglutinated after treatment with trypsin or chymotrypsin. Specific agglutination was again possible after incubation for 5 h at 37 degrees C in the absence of enzyme. (vi) CBD covalently linked to crosslinked agarose beads inhibited interleukin 2 production by phorbol ester-stimulated EL-4 cells. No activity was seen if cell-to-bead contact was prevented by a 0.02-microns microporous filter that did not interfere with the passage of CBD. Our findings support the presence of a functional receptor on the surface of selected cells of the immune system.
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PMID:Evidence for a functional receptor for cyclosporin A on the surface of lymphocytes. 158 69

We report a case of cutaneous T cell lymphoma (CTCL) treated with local injection of recombinant interleukin 2 (rIL-2). The biopsy specimen showed marked infiltration of large convoluted cells admixed with small lymphocytes and histiocytes in the epidermis, dermis and subcutis. After six injections of rIL-2, 4 nodules out of 5 on the left lower leg disappeared and the remaining large nodule was diminished in size. A biopsy specimen from the diminished nodule showed infiltration of small lymphocytes with histiocytes and plasma cells in the dermis. The atypical cells, large hyperconvoluted lymphocytes, had disappeared. A large number (28%) of lysozyme- and alpha 1-anti-chymotrypsin-positive cells were demonstrated by immunohistochemistry. The patient maintained complete remission for a period of 13 months. He then noticed a small red nodule on the back of the left foot, which was histologically confirmed as a recurrence. Chemotherapy cleared the lesion.
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PMID:A case of cutaneous T cell lymphoma treated with recombinant interleukin 2 (rIL-2). 246 89

A cell surface antigen (gp140) was previously shown to exist on T cell subsets as well as on monocytes and macrophages in normal peripheral blood. Elevated expression of this antigen was associated with immune system disorders, acute lymphocytic leukemias, and in vitro activation of T cells. The antigen could be identified with monoclonal antibody (MAb) T305. Gp140 was a biosynthetic product of T cells because it could be labeled with [3H]leucine or [3H] glucosamine. Biochemical studies of gp140 used high performance liquid chromatography with nitrocellulose blotting to isolate aliquots suitable for 125I radiolabeling and immunoprecipitation to demonstrate: a) a reduction in m.w. of gp140 KD to 90 KD after deglycosylation by trifluoromethanesulfonic acid, b) alteration of isoelectric point from 4.1 to 5.7 after neuraminidase treatments, c) absence of N-linked sugars based on resistance to endoglycosidase F, d) resistance to trypsin and chymotrypsin digestion but susceptibility to pronase, and e) presence of sialic acid and lactosaminoglycan as O-linked sugars. Gp140 could be labeled with the periodate/NaB[3H]4 technique, indicating its similarity to a class of sialoglycoproteins previously described on activated T-cells in mouse and man. The antigenic epitope recognized by MAb T305 contains sialic acid linked (2----3) to galactose; however, periodate oxidation of the exocyclic ring of sialic acid did not affect binding by MAb T305. In an attempt to determine the functional role of gp140, we tested the ability of MAb T305 to block: a) proliferation of peripheral blood lymphocytes to mitogens, b) response to interleukin 2 (IL 2) of an IL 2 dependent T cell line, and c) growth of a T-ALL derived cell line. No inhibition of proliferation or growth was noted. Although the function of gp140 remains unknown, its association with lymphocyte activation and certain disease states suggests that it may provide a target for modulation of the immune response. These studies characterize the structural features of gp140 and further define the epitope recognized by MAb T305.
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PMID:Characterization of a membrane surface glycoprotein associated with T-cell activation. 298 44

We have succeeded in isolating a rat myelomonocytic leukemia cell line (c-WRT-7) that is capable of producing a factor with biological and biochemical properties similar to those ascribed to interleukin 1 (IL-1). Lipopolysaccharides (LPS), phorbol myristate acetate (PMA) and mezerein were found to be capable of inducing c-WRT-7 cells to secret IL-1, while non-stimulated c-WRT-7 cells were unable to produce any IL-1 whatever. After treatment of c-WRT-7 cells with LPS, IL-1 activity reached a maximum level after approximately 48 hrs of culture. Supernatants from LPS-stimulated c-WRT-7 cells promoted the proliferation of thymocytes initiated by suboptimal doses of lectins, and restored depressed mitogenic responses of macrophage depleted spleen cells. However, no detectable interleukin 2 (IL-2) activity was observed in the supernatants of LPS-stimulated c-WRT-7 cells. The IL-1 from c-WRT-7 cells had an apparent molecular weight between 15,000 and 20,000 when measured by gel filtration. The thymocyte comitogenic activity was maintained mainly at alkaline pH and the reduction was noted at the pH below 4. The activity was partially inactivated by heating at 60 degrees C for 60 min or at 70 degrees C for more than 10 min. Papain and pronase reduced the activity completely, whereas chymotrypsin and trypsin had little effect. To our knowledge this is the first established rat myelomonocytic leukemia cell line that has been found to be capable of producing IL-1.
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PMID:The production of interleukin 1 by a differentiating rat myelomonocytic leukemia line. 326 May 72

The killing of Fischer rat 9L glioma in vitro by lymphokine-activated killer (LAK) cells was studied. LAK cells generated by culturing Fischer spleen cells with recombinant interleukin 2 markedly lysed glioma cells but did not kill syngeneic normal brain tissue in a chromium release microcytotoxicity assay. Susceptibility of glioma to lysis by LAK cells was markedly diminished by pretreating the glioma cells with trypsin or chymotrypsin but was unaffected by pretreatment with neuraminidase, glycosidases, or sodium periodate. These results suggest that LAK cell killing of glioma is probably tumor-selective and that a crucial cell surface determinant on glioma cells responsible for its tumor-selective lysis by LAK is a protein sensitive to trypsin and chymotrypsin.
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PMID:Lymphokine activated killer (LAK) cell-mediated lysis of murine glioma: trypsin-chymotrypsin-sensitive glioma protein is responsible for tumor-selective recognition by LAK cells. 348 96

The human monocytic leukemia cell line THP-1 produces an immunosuppressive factor that inhibits interleukin 1 (IL-1)-dependent proliferation of mouse thymocytes as well as the mitogenic effects of concanavalin A (Con A) and phytohemagglutinin (PHA) on human peripheral blood mononuclear cells. The mechanism of action of this factor includes interference with both the production of interleukin 2 (IL-2) and its effects on target cells. Thus, the suppressor abrogates the proliferation of an IL-2-dependent cytotoxic T cell line (CTLL), but not of IL-2 independent cells like the L929 fibroblasts or the EL4 T lymphoma and U937 histiocytic lymphoma lines. It also suppresses IL-2 production by human peripheral blood enriched T cells and mouse splenocytes. The mediator has a molecular weight of 60,000-70,000 dalton, as determined by gel filtration chromatography, is heat labile, and is sensitive to trypsin, chymotrypsin, and protease.
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PMID:A macrophage-derived factor that inhibits the production and action of interleukin 2. 389 22

We previously demonstrated the development of a cloned human T cell hybridoma that secretes B cell growth factor (BCGF) in the absence of demonstrable interleukin 2 or B cell differentiation factor. Sephadex gel filtration chromatography demonstrated the m.w. of this factor to be 18 to 20K. The present studies were performed to further characterize the biochemical properties of the molecule and to determine its target cell specificity. Temperature stability studies showed the monoclonal BCGF to be stable at 37 degrees C for 12 hr and at 70 degrees C for 15 min; however, most (93%) of the activity was lost after incubation at 70 degrees C for 30 min. Aliquots of hybridoma supernatant were exposed to buffer solutions with variable pH with no diminution in activity over a pH range of 4.0 to 10.0 BCGF activity was not affected by 2-mercaptoethanol, neuraminidase, or nucleic acid denaturing enzymes. In contrast, all activity was destroyed by 10 M urea, trypsin, and chymotrypsin. Chromatofocusing demonstrated the isoelectric point of BCGF to be 6.3 to 6.6. Finally, absorption experiments demonstrated that BCGF activity was absorbed by large, activated B cells. Mitogen-stimulated T cell blasts, small resting B cells, and CESS cells failed to absorb BCGF activity from the hybridoma supernatant. These and future studies with purified monoclonal human BCGF should enhance our understanding of its immunochemical properties and of its role in the immunoregulation of human B cell responses.
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PMID:Characterization of monoclonal B cell growth factor (BCGF) produced by a human T-T hybridoma. 642 36