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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased production of the serum protease plasminogen activator is associated with tissue damage. The in vitro production of plasminogen activator by alveolar macrophages obtained by bronchoalveolar lavage was studied in 22 normal subjects and 28 patients with interstitial lung disease to determine whether plasminogen activator is produced by normal alveolar macrophages and whether this is increased in patients with interstitial lung disease. Plasminogen activator activity, measured with an iodine-125 labelled fibrin release assay, was found to be dependent on time, effector cell numbers, and plasminogen concentration. Plasminogen activator production by alveolar macrophages from 14 normal non-smokers and eight normal smokers was similar and the mean value was 0.78 (SEM 0.16) urokinase (UK) units x 10(-8)/cell/hour. Alveolar macrophages from the seven patients with cryptogenic fibrosing alveolitis and six patients with histiocytosis-X produced more plasminogen activator (1.89 (0.25) and 4.54 (1.3) x 10(-8) UK units/cell/hour respectively) than macrophages from normal subjects (p less than 0.05), whereas those from 15 patients with sarcoidosis did not (1.09 (0.2) x 10(-8) UK units/cell/hour). Exposure of normal alveolar macrophages to immune complexes enhanced plasminogen activator production to 2.07 (0.27) x 10(-8) UK units/cell/hour, whereas exposure to products of activated T cells and to purified gamma interferon reduced plasminogen activator production (to 0.38 (0.11) and 0.62 (0.11) x 10(-8) UK units/cell/hour respectively). These studies show that plasminogen activator is produced by normal human alveolar macrophages and that its production is increased in patients with cryptogenic fibrosing alveolitis and histiocytosis-X.
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PMID:Production of plasminogen activator by alveolar macrophages in normal subjects and patients with interstitial lung disease. 321 49

In the presence of a colony-stimulating factor, murine bone marrow cells proliferate and differentiate into macrophages. This culture system was taken as a model to study the expression of various functions by macrophages in the course of maturation. Several tests were performed daily and in parallel from the same batch of cells. It was found that certain functions were expressed early and were also characteristic for mature macrophages such as Fc receptors, phagocytosis of latex beads and unspecific esterase activity. Other functions appeared and disappeared in an ordered sequence, such as the response to macrophage migration inhibitory factor and chemotactic factor as well as the production of interferon and of plasminogen activator. The time course of functional expression was strongly dependent on proliferation of precursor cells as well as proliferation of differentiated macrophages. It is suggested that the phenotypic expression of functions during differentiation is the basis for the functional heterogeneity of macrophages.
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PMID:Sequential expression of functions during macrophage differentiation in murine bone marrow liquid cultures. 616 25

Macrophage migration inhibitory factors (MIFs) of mouse and guinea pig have been thoroughly characterized with regard to molecular weight and isoelectric points. Several molecular weight species have been identified. In a comparative study with purified MIFs it was found that these molecules were distinct from a series of other lymphokines, particularly so from macrophage activating activities. Investigations on the molecular weight heterogeneity of MIF have led us to a transglutaminase-like activity which was found to be expressed in certain subsets of macrophages. The question whether low molecular weight factors are polymerized by this enzyme to oligomers is further investigated. Studies on the induction by lymphokines of interferon and plasminogen activator revealed a great heterogeneity of responding macrophages. In studies on the biological basis of the functional heterogeneity of macrophages, the question was investigated whether the heterogeneity was due to different macrophage subpopulations or to intermediate relatively stable phenotypes on their way to maturity and senescence. To approach this question, the bone marrow liquid culture system was used as a developing system. Our data are summarized in a unifying model which takes into account the different constitutive and inducible functions during the cell cycle. Accordingly, lymphokines may act either as differentiation signals, as mitogens or activating signals.
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PMID:Modulation of macrophage functions by lymphokines. 617 79

Macrophages which are intimately involved in acute and chronic inflammatory reactions are functionally heterogeneous not only with regard to the expression of constitutive functions but also in their response to lymphokine signals. The biological basis of this heterogeneity is poorly understood. Whether we are dealing with true subpopulations or with intermediately stable phenotypes has not been resolved. To study these questions we adopted a bone marrow liquid culture system in which bone marrow cells--in the presence of a colony-stimulating factor--proliferate and differentiate into macrophages. This culture system was taken here as a model to study the expression of various functions by macrophages in the course of maturation. Several tests were performed daily and in parallel from the same batch of cells. It was found that certain functions were expressed early and were also characteristic for mature macrophages such as Fc receptors, phagocytosis of latex beads and unspecific esterase. Other functions appeared and disappeared in an ordered sequence, such as the response to macrophage migration inhibitory factor and chemotactic factor as well as the production of interferon and plasminogen activator. The time course of functional expression was strongly dependent on proliferation of precursor cells as well as on proliferation of differentiated macrophages. It is concluded that the transient phenotypic expression of functions during differentiation is the basis for the functional heterogeneity of macrophages.
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PMID:Heterogeneity of macrophages in response to lymphokines and other signals. 618 13

The purpose of this work was to study the interrelationship of proliferation and secretion of plasminogen activator (PA) and interferon (IFN) by murine macrophages. For induction of macrophage proliferation and secretion of PA, concanavalin A (Con A) was used. Secretion of IFN was induced by polyinosinic polycytidylic acid complex. The glucocorticoid dexamethasone acetate (DA) (10(-6)-10(9) M) inhibited Con A-stimulated secretion of PA and synthesis of DNA as evaluated by incorporation of [3H]thymidine. DA did not inhibit IFN induction. Preincubating macrophages with DA for 45 h reduced basal proliferation and secretion of PA but did not reduce responsiveness to Con A. Also retinoic acid, a modulator of carcinogenesis was used in inhibition studies because of its known antagonistic effects on lymphocyte mitogenesis. In macrophages a biphasic effect of retinoic acid (1 X 10(-5) - 5 X 10(-5)M) was found: (a) inhibition of DNA synthesis and secretion of PA during the first 45 h of incubation, and (b) enhancement of DNA synthesis (but not PA secretion) after 72 h. Secretion of IFN was not affected. It is suggested that secretion of PA but not IFN is linked to cell cycle traverse of macrophages.
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PMID:Regulation of plasminogen activator secretion, interferon induction and proliferation in murine macrophages. 618 80

Purified mouse T lymphocytes were separated into Lyt-2+ and Lyt-2- populations by the procedure of panning, in which a monoclonal rat anti-Lyt-2 antibody and dishes coated with affinity-purified mouse anti-rat Ig antibodies were used. The populations obtained were 95 to 99% pure as determined by immunofluorescence. Graded doses of these T cells were cultured with optimal mitogenic doses of concanavalin A and the 0 to 24 and 24 to 48-hr culture supernatants were collected. The dose-curve assays of the supernatants of Lyt-2+ and Lyt-2- cells showed comparable activity in interleukin 2 (IL 2) and T cell-replacing factor (TRF), assayed on antigen-stimulated culture of T-depleted spleen cells. Limiting dilution assays of IL 2-secreting precursor cells stimulated by Con A showed a high frequency of precursors in both populations, slightly higher among Lyt-2- cells. The supernatants also contained comparable levels of IPA (inducer of plasminogen activator production by the macrophages), MAF (macrophage-activating factor, assayed by induction of their cytolytic function), and MCGF (mast cells growth factor, assayed on a mast cell line). IPA and MAF were not produced with the same kinetics and in the same T cell concentration conditions as IL 2 and TRF. In contrast, interferon was principally produced by the Lyt-2+ cells.
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PMID:Positively selected Lyt-2+ and Lyt-2- mouse T lymphocytes are comparable, after Con A stimulation, in release of IL 2 and of lymphokines acting on B cells, macrophages, and mast cells, but differ in interferon production. 618 45

Cell line CEC-32 and clone LSCC-H32 were established from primary chicken embryo cells spontaneously but not experimentally transformed at 32 degrees C. The lines consisted of fibroblastoid and polygonal cells and had a subtetraploid karyotype of 2N = 130 to 140. The cells showed increased plating efficiency and metabolic activities as demonstrated by hexose uptake and plasminogen activator assay. The established cells produced avian lymphoid leukosis viruses of subgroups A and B. The virus released from LSCC-H32 cells induced lymphoid leukosis in inoculated chickens 18 to 22 wk post infection (PI). The cells have been carried in continuous culture for 285 passages and they appeared to grow indefinitely. They were efficiently used to propagate several animal viruses and to titrate chicken interferon.
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PMID:Establishment and characterization of chicken embryo fibroblast clone LSCC-H32. 629 61

Monocyte or macrophage polykaryons (MP) are seen in different tissues in various inflammatory states and in normal bone (osteoclasts). The factors controlling the formation and the function of MP are not completely understood. This study was designed to evaluate the effects of the lymphokine gamma-interferon (IFN-gamma) on human monocyte function in vitro. Purified recombinant IFN-gamma [20-200 units/ml (0.1-1.0 nM)] caused the appearance of MP in cultures of normal human monocytes cultured in 10% unheated autologous serum. The MP were noted by as early as 36 hr of culture with fusion indices of 40%-60% and up to 160 nuclei per cell. The effect was seen with both recombinant IFN-gamma and natural IFN-gamma produced by Staphylococcal enterotoxin A-stimulated lymphocytes, but IFN-alpha (leukocyte-derived and recombinant) and IFN-beta did not induce MP formation. The activity of the IFN-gamma was destroyed by heating at 56 degrees C for 4 hr, incubating at pH 2 for 3 hr, or incubating with antibody against IFN-gamma. Populations of monocytes incubated 3 days with 100 units of IFN-gamma per ml (0.5 nM) had enhanced capacity to produce H2O2 in response to phorbol 12-myristate 13-acetate and increased content of acid phosphatase and plasminogen activator. As determined by autoradiography, the MP did not incorporate [3H]dThd into their nuclei. Thus, the IFN-gamma appears to induce MP formation by a process of monocyte fusion, and to "activate" monocytes, as judged by various parameters.
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PMID:Recombinant human gamma-interferon induces human monocyte polykaryon formation. 643 9

The human diploid fibroblast cell line, MRC-5, derived from embryo lung tissue produced only small quantities of plasminogen activator (PA) when harvested using a standard nutrient medium (Eagle's Minimal Essential Medium, MEM). Use of a schedule designed to induce high concentrations of fibroblast interferon in these cells also resulted in production of considerably enhanced levels of PA. The kinetics of PA production differed from those of interferon production; specifically, PA was produced for at least 6 days following induction despite the toxicity of the inducers whereas interferon synthesis continued for only 1 day. Further investigation of the induction conditions for PA revealed that double-stranded RNA which was absolutely required for interferon production was not required for induction of PA. Indeed, the stimulus for enhancement of PA production appeared to be solely an elevated concentration of calcium ions in the extracellular medium. The possible physiological relevance of this induction of PA by elevated concentrations of calcium ions is discussed.
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PMID:Induction of plasminogen activator in a human diploid fibroblast cell line (MRC-5) by conditions which cause induction of interferon: the role of calcium ions. 653 47

Macrophages and monocytes become activated, by a variety of mechanisms, to exhibit cytotoxicity. Associated with this activation for cytotoxicity is the production of certain neutral proteases, especially plasminogen activator (PA), which may be involved in the mechanism of cytolysis. Supernatants from concanavalin A (Con A) or antigen-stimulated spleen cells contain factor(s) which render macrophages and monocytes activated in vitro (MAF/MIF). We have found that in addition to such spleen cell supernatants murine interferon was able to activate peptone-induced C57BL/6 peritoneal macrophages to produce PA but had no effect on human monocytes. Similarly, human recombinant interferon activated human monocytes but not murine macrophages to produce PA. In addition to displaying this species specificity, interferon was able to function as a monocyte/macrophage activator in this system just as in cytotoxicity and may be a regulator of monocyte/macrophage function in vivo by modulation of proteolytic enzymes.
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PMID:Interferon activates macrophages to produce plasminogen activator. 689 86


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