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

Human monocytes, but not nylon wool column-nonadherent lymphocytes, produce plasminogen activator. The activity is found only in association with intact cells. Exposure of monocytes to activated lymphocytes or to lymphokine-rich supernatants enhances monocyte plasminogen activator production. The assay allows assessment of baseline and activated human monocyte function.
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PMID:Plasminogen activator production by human monocytes. I. Enhancement by activated lymphocytes and lymphocyte products. 50 Oct 90

We describe a sensitive assay to measure immune activation of human macrophages in cell culture. Freshly isolated blood monocytes from normal subjects lack the ability to endocytose and degrade mannosyl-terminated glycoconjugates via specific receptors, but acquired this activity after cultivation in autologous serum for approximately 3 d. Addition of specific antigen, purified protein derivative, or T cell mitogens to mononuclear cells prevented the appearance of macrophage mannosyl receptor activity and lymphokine, gamma-, and alpha-interferons selectively down-regulated receptor activity in monocyte-macrophage targets. The effects of antigen challenge and gamma-interferon on mannosyl receptors can be prevented by 10(-8) M dexamethasone. Dexamethasone also inhibited release of another macrophage activation marker, plasminogen activator, which was increased by both gamma- and alpha-interferons. These studies show that activation of human macrophages is regulated by opposing actions of lymphokines and glucocorticoids.
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PMID:Human macrophage activation. Modulation of mannosyl, fucosyl receptor activity in vitro by lymphokines, gamma and alpha interferons, and dexamethasone. 257 1

The effects of lymphokine production of two agents known to potentiate delayed-type hypersensitivity (DTH), pertussigen (pertussis toxin) (PT) and cyclophosphamide (CY) have been investigated. These two agents were administered to immunized mice. Subsequently, lymph nodes and spleen cells were exposed to specific antigen in vitro. The resulting culture supernatants were assayed for the presence of lymphokines. Only supernatants of cells from the mice given PT contained appreciable quantities of interferon-gamma (IFN-gamma) and stimulated cells of the monocyte-like WEHI-265 cell line to produce procoagulant activator and plasminogen activator. On the other hand, CY was more effective than PT on the production of interleukin-3 (IL-3). Both adjuvants had small enhancing effects on the production of interleukin-2 (IL-2). With either adjuvant, the cell populations induced had a similarly enhanced capacity to transfer DTH. These results demonstrate that the capacity of cells to transfer DTH does not necessarily correlate with their release of particular lymphokines. The potentiation of DTH by cyclophosphamide did not depend on significantly enhanced generation of IFN-gamma, procoagulant activator, or plasminogen activator. The amount of IFN-gamma in the culture supernatants correlated with their capacity to produce procoagulant activator and plasminogen activator, whereas the amount of IL-2 and IL-3 did not.
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PMID:Potentiation of delayed-type hypersensitivity by pertussigen or cyclophosphamide with release of different lymphokines. 312 25

Pertussigen is a protein toxin of Bordetella pertussis that acts as a powerful stimulator of the intensity and duration of delayed-type hypersensitivity (DTH) in mice. This study describes the potent in vivo effect of pertussigen on the levels of antigen-specific macrophage-activating lymphokine(s); lymphokine(s) was measured by the stimulation of macrophage procoagulant activity (mPCA), or plasminogen activator (PA) activity. Lymphoid cells were removed from immunized animals and cultured with specific antigen, keyhole limpet hemocyanin, ovalbumin, or human gamma-globulin. The culture supernatants were then incubated with the monocyte-like cell line WEHI-265 to measure mPCA or with WEHI-265 or resident peritoneal macrophages to measure PA activity. Mice were given pertussigen at the time of immunization, and the subsequent generation by lymphocyte supernatants of both of these macrophage activities proved to be greatly enhanced; the effect of pertussigen was antigen specific. Pertussigen thus induces an increase in lymphokine(s) production responsible for the in vitro increase in macrophage mPCA and PA activity and which may be responsible for some of the potent immune effects of this agent in vivo.
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PMID:Pertussigen in vivo enhances antigen-specific production in vitro of lymphokine that stimulates macrophage procoagulant activity and plasminogen activator. 378 90

Long-term cultures of pig aortic endothelial (E) cells secrete plasminogen activator (PA). When these cells were cultured with murine lymphokine(s) produced in response to antigen, mitogen, or allogeneic stimuli, there was consistently increased PA secretion by E cells. The evidence suggests that initiator of plasminogen activator (IPA) is produced by a nylon-wool--nonadherent cell, probably a T cell. The kinetics of this activation of PA suggest that the effect of IPA on E cells is considerably delayed compared with that on phagocytic cells. The significance of these findings is discussed in terms of their possible relationship to several immunopathological states.
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PMID:Enhancement of endothelial plasminogen activator synthesis by lymphokines. 387 17

Rabbit alveolar macrophages can directly stimulate either coagulation or fibrinolysis by producing tissue thromboplastin and plasminogen activator activities, respectively. However, it is not known whether these 2 opposed physiologic activities are expressed by the same or different cells within a population of alveolar macrophages. This study was undertaken to determine the distribution of procoagulant and plasminogen activator activities among density-defined populations of rabbit alveolar macrophages. Normal rabbit alveolar macrophages were separated into 4 density fractions on continuous gradients of Percoll, and the distribution of procoagulant and plasminogen activator activities among these fractions was determined. The procoagulant activity of the least dense cells (Fraction 1) was as much as 6 times greater than the activity displayed by denser cells (Fractions 2 to 4). By contrast, both cell-associated and secreted plasminogen activator activities were equally and uniformly distributed among all density fractions. These distributions of activities among density fractions persisted after the cells were incubated in culture medium for 24 h. After culture in vitro with lymphokine, procoagulant activity increased in the denser cells so that the activity became equal among all density fractions. We conclude that procoagulant activity distributes differently from plasminogen activator activity among fractions of normal rabbit alveolar macrophages separated according to cell density. By using density gradient fractionation, alveolar macrophages with predominantly procoagulant or plasminogen activator activities can be enriched from the lavage cell population; the dissimilar distribution of these 2 activities within the alveolar macrophage cell population does not reflect the presence of cells with fixed differences in their functional capacities.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The distribution of procoagulant and plasminogen activator activities among density fractions of normal rabbit alveolar macrophages. 395 54

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

Human peripheral monocytes stimulated by either muramyl dipeptide [N-acetyl-muramoyl-L-alanyl-D-isoglutamine], bacterial lipopolysaccharide or lymphokine-containing supernatants of human lymphocytes, could be shown to produce and secrete appreciable activities of a 52 000-Mr plasminogen activator. This enzyme was suppressed in control and stimulated cultures by dexamethasone (0.1 microM). Monocyte plasminogen activator could only be assayed under conditions of low ionic strength and had no detectable activity at 0.15 M NaCl. Intracellular enzyme was present as a proenzyme, requiring activation by preincubation with plasminogen containing traces of plasmin, before its activity could be seen on sodium dodecyl sulphate/polyacrylamide gel electrophoresis by a fibrin overlay method. Secreted enzyme was in the active form. Further incubation of lysate or supernatant plasminogen activator with plasminogen did not produce any active enzyme species of Mr 36 000, unlike incubations of urokinase with plasminogen. Moreover, comparisons with other plasminogen activators of Mr 52 000 from transformed cell lines showed that the monocyte activator was unique in its resistance to monocyte minactivin, a specific inactivator of urokinase-type plasminogen activators, and in its sensitivity to human alpha 2-macroglobulin. It was therefore concluded that human monocyte plasminogen activator, although sharing an Mr of 52 000 in common with other such activators, is not identical to the high Mr form of urokinase or the plasminogen activators of transformed cells. On present evidence it is the least likely of these enzymes to be active extracellularly under normal physiological conditions.
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PMID:Novel properties of human monocyte plasminogen activator. 619

Murine mononuclear phagocytes in various stages of activation were elicited in vivo or induced in vitro. The cytolytic competence of each type of macrophage, before and after treatment with traces of endotoxin, was quantified. Populations of responsive, primed, and activated macrophages, but not resident macrophages, expressed five markers that have been reported to characterize inflammatory macrophages: increased spreading, increased phagocytosis via Fc and C3 receptors, increased secretion of plasminogen activator, and decreased content of the ectoenzyme 5' nucleotidase. Primed macrophages secreted cytolytic protease (CP) when pulsed with traces of endotoxin; the resident and responsive macrophages did not. The primed macrophages bound tumor cells to a considerable degree; the resident and responsive macrophages did not. The cytolytically activated macrophages bound tumor cells well and secreted lytic protease spontaneously. The capacity for augmented, selective binding of tumor cells is apparently induced in only one step by application of lymphokine(s). The capacity for secreting CP, however, is regulated in two steps; initial priming signals--lymphokine(s)--prepare the macrophages for secretion, and a second signal, such as endotoxin or endotoxin plus tumor cells, triggers the actual release of CP.
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PMID:Sequential activation of murine mononuclear phagocytes for tumor cytolysis: differential expression of markers by macrophages in the several stages of development. 630 3

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


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