Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Administration of the synthetic estrogen diethylstilbestrol (DES) lowers the systemic resistance of mice to challenge with either tumor cells or the facultative intracellular parasite Listeria monocytogenes. To assess the potential role of impaired mononuclear phagocyte system (MPS) function in this depression of host resistance, we addressed the question of systemic perturbations of the MPS induced by administration of DES. A panel of objective quantitative markers which have been previously shown to identify and characterize macrophages in the several stages of development of activation was employed. DES perturbed the resident population of peritoneal macrophages by increasing their number approximately twofold and by enhancing their competence for phagocytosis, cytostasis of tumor cells, and secretion of plasminogen activator. When we examined the competence of the MPS in DES-treated mice to respond to challenge with activating stimuli, we found that DES systemically suppressed the development of macrophages, in response to either pyran copolymer or BCG, to develop tumoricidal function and to gain competence for secretion of reactive oxygen intermediates such as H2O2. Since these data suggested that DES inhibited the development of macrophages from a precursor stage (i.e., responsive macrophages) to activated macrophages in vivo, we tested this possibility directly by applying known activating signals in vitro to responsive macrophages. Responsive macrophages from DES-treated mice did not become activated in response to the application of two known potent activating signals (i.e., MAF + LPS). Taken together, the data indicate that DES systemically perturbs the MPS and does so by enhancing development of the early stages of maturation and suppressing subsequent development.
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PMID:Functions of mononuclear phagocytes in mice exposed to diethylstilbestrol: a model of aberrant macrophage development. 380 3

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

Macrophages are heterogeneous with respect to a number of constitutive and inducible functions. In order to study the underlying biological principle, a bone marrow liquid culture system was adopted in which bone marrow cells proliferate and differentiate into macrophages. It was found that maturing macrophages express various constitutive or inducible functions in an ordered sequence. The kinetics of their appearance and disappearance are dependent on the proliferative activity of macrophages. Macrophages in "late" G-1 of the cell cycle express constitutive functions like plasminogen activator production and are inducible by bacterial lipopolysaccharides, Poly I:C and lymphokines to release interferons. The response to lymphokines like migration inhibitory factor (MIF) and chemotactic factors is also transiently expressed during maturation. Using purified MIF, its influence on proliferation, differentiation and activation of macrophages was investigated. The changes induced were monitored following the expression of marker enzymes and of phenotype associated cell surface antigens using monoclonal antibodies. The results showed that functional changes induced by MIF on macrophages are limited and are not related to certain macrophage activating activities (MAF). As determined by flow cytofluorometry, transglutaminase expression and proliferation is consistently down-regulated by MIFs. This together with the shift and the expression of surface antigens indicates that MIFs provide a differentiation signal for a "young" macrophage to become more mature.
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PMID:[Chemical and functional characterization of lymphokines]. 623 26

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