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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potential role of platelet-activating factor (PAF)-acether and of IL-5 as an eosinophil-proliferating, activating, and/or recruiting mediator in asthma led us to study the effects of human (h) rIL-5 (hrIL-5) and PAF-acether, alone or combined, on isolated guinea pig eosinophils. Two populations of eosinophils were separated from peritoneal lavages of polymyxin B-treated guinea pigs upon a discontinuous metrizamide gradient: one of low density (between 20 and 22% of metrizamide, purity: 63 +/- 3%, n = 27) and another of normal density (between 22 and 24% of metrizamide, purity: 87 +/- 2%, n = 16). Chemotactic activity was evaluated on a micro-Boyden chamber, results being expressed as the number of migrating eosinophils (mean +/- SEM) at 40 microns through a cellulose nitrate filter (3 microns pore size) in the presence of the agonist or of the solvent alone. hrIL-5 dose-dependently stimulated normodense eosinophil chemotaxis, reaching a peak at 500 ng/ml (98 +/- 21 migrating eosinophils, n = 5, p less than 0.05). These eosinophils also responded to PAF-acether and to LTB4 and not to FMLP, hrTNF alpha, and LPS. Eosinophil preincubation with hrIL-5 increased significantly the migration by PAF-acether (173 +/- 23 migrating eosinophils with PAF-acether 10 nM after preincubation with hrIL-5 500 ng/ml vs 69 +/- 10 after preincubation with buffer alone, p less than 0.01) and failed to enhance migration by LTB4 or to uncover an activity for FMLP. Migration by PAF-acether was antagonized when the cells were preincubated with the antagonists BN 52021 and WEB 2086, which also inhibited migration by hrIL-5. Eosinophils were auto-desensitized by and to PAF-acether or LTB4, but were not cross-desensitized to each other. Eosinophils desensitized to PAF-acether failed to migrate with hrIL-5, but those desensitized to LTB4 responded to hrIL-5 as controls. hrIL-5 failed to induce the elevation of intracellular free calcium concentration and superoxide anion generation from basal values, whereas preincubation of eosinophils with hrIL-5 induced a significant increase in the rise in intracellular free calcium concentration and in superoxide anion generation by 10 nM PAF-acether but not by LTB4. In conclusion, the in vivo eosinophil migration in allergy may involve hrIL-5, particularly associated to PAF-acether.
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PMID:Activation of guinea pig eosinophils by human recombinant IL-5. Selective priming to platelet-activating factor-acether and interference of its antagonists. 165 95

We investigated alterations in myocardial beta- and beta 1-adrenergic receptor (BAR and B1AR) number during hyperdynamic state induced by endotoxin or cytokines. [METHODS] Twenty-nine Japanese White rabbits were divided into 2 groups. Hearts were removed 18 h after intraperitoneal administration of sterile saline (SAL) or E. coli endotoxin (LPS; 50 micrograms/kg) (Group E, n = 12), or 3 h after intravenous injection of SAL or cytokines (interleukin 1-beta; 5 micrograms/kg followed by 25 ng/kg/min for 2 h, or tumor necrosis factor; 5 micrograms/kg) (Group C, n = 17). BAR and B1AR numbers were determined in myocardial membranes from rabbit left ventricles with techniques of radioactive ligand binding study. We used [3H] dihydroalprenolol (3H-DHA) as radioactive ligand, and specific 3H-DHA binding to BARs was defined as the difference between the presence and the absence of 10 microM propranolol. B1AR number was assessed through the specific binding of 3H-DHA in the presence of ICI 118, 551 (5 x 10(-8) M), a highly selective beta 2-adrenergic receptor antagonist. In Group E, mean arterial blood pressure (MAP), heart rate (HR), and cardiac output (CO) (by thermodilution) were measured under pentobarbital sodium anesthesia before excision of hearts. [RESULTS] In Group E, CO was significantly (p less than 0.05) increased in rabbits injected with LPS (E-LPS) as compared with that in rabbits injected with SAL (E-SAL) (E-LPS; 0.75 +/- 0.02 l.min-1, E-SAL; 0.61 +/- 0.05 l.min-1, mean +/- SEM). MAP and HR were slightly decreased in E-LPS but not significantly. Maximum binding (Bmax) of 3H-DHA to BARs was significantly (p less than 0.05) decreased by 18% in myocardial membranes from E-LPS compared to E-SAL (E-LPS; 48.2 +/- 4.3 fmol/mg protein, E-SAL; 58.9 +/- 2.9 fmol/mg protein, mean +/- SEM). Similarly, Bmax of 3H-DHA to B1ARs was decreased by 18% in E-LPS, although no statistical significance was detected. In Group C, both BAR and B1 AR number was slightly, but not significantly decreased 3 h after administration of cytokines. [CONCLUSION] These data suggest that down regulation of cardiac BARs may occur during hyperdynamic stage of endotoxic shock.
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PMID:[Alterations in number of rabbit myocardial beta-adrenergic receptors in endotoxic shock: down regulation in hyperdynamic sepsis model and effects of cytokines administration]. 166 39

The number and function of pulmonary macrophages are critical to lung homeostasis. To characterize factors normally present in the human respiratory tract that can influence these parameters, bronchoalveolar lavage (BAL) fluid obtained from healthy smokers and nonsmokers was assayed for the presence of colony-stimulating factor (CSF) activity. Concentrated BAL fluid from both populations was capable of inducing incorporation of [3H]thymidine by murine macrophages. The mean increase (+/- SEM) in incorporation over control cultures not exposed to BAL fluid was 0.98 +/- 0.22 for nonsmokers and 2.25 +/- 1.19 for smokers (p less than 0.001). This CSF bioactivity was characterized as macrophage-CSF (M-CSF) by virtue of its action on murine macrophages, the detection of M-CSF protein by a specific ELISA assay, and the inability to detect other macrophage-active CSFs, granulocyte macrophage-CSF (GM-CSF) and interleukin-3 (IL-3), in a proliferation assay employing the MO7E cell line. There was a significant correlation between macrophage number in BAL samples and measureable bioactivity among both smokers and nonsmokers (r = 0.763; p less than 0.001). This suggested that macrophages themselves are a source of the M-CSF detected in BAL fluid. To examine this possibility, slot-blot analysis of macrophage RNA was performed. Constitutive expression of comparable amounts of M-CSF mRNA and protein was found in cells from both smokers and nonsmokers. However, macrophages obtained from a randomly selected subset of four smokers but none of five nonsmokers exhibited increased production of M-CSF in response to an inflammatory stimulus, lipopolysaccharide (LPS; 5 ng/ml). M-CSF added to macrophage cultures was degraded by nonsmokers' cells as expected over 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of colony stimulating factor activity in the human respiratory tract. Comparison of healthy smokers and nonsmokers. 173 48

We studied the release of tumor necrosis factor-alpha (TNF alpha), a vital immunoregulatory cytokine, by alveolar macrophages (M phi s) infected with simian immunodeficiency virus (SIV) in vitro or collected from SIV-infected macaques. For in vitro studies, M phi s were harvested by bronchoalveolar lavage from 5 normal animals and infected in flasks with SIV (10(4)TCID50/2.5 x 10(6) M phi s). After 7 to 10 days, cytopathic effect was prominent and 68 +/- 2% of M phi s were immunoreactive for p27 core protein. Uninfected (control) and SIV-infected M phi s were then cultured for 24 hours in 96-well plates (10(5) M phi s/well) while challenged with lipopolysaccharide (LPS; 100 micrograms/ml). TNF alpha was assayed in culture supernatants by an enzyme-linked immunosorbent assay (detection limit, 50 pg/ml) and results were expressed as pg TNF alpha/ml/10(3) M phi s (mean +/- SEM). TNF alpha was not detected in unstimulated wells. TNF alpha release by control and SIV-infected M phi s was similar (6.6 +/- 0.7 and 7.9 +/- 1.1 pg/ml/10(3) M phi s, respectively). We also studied TNF alpha release by alveolar M phi s from 8 animals infected with SIV (3 asymptomatic, 5 with acquired immune deficiency syndrome virus (AIDS]. One animal with AIDS had p27+ M phi s. Alveolar M phi s from asymptomatic animals released significantly more TNF alpha (10.3 +/- 1.1 pg/ml/10(3) M phi s) than did animals with AIDS or uninfected macaques (5.2 +/- 0.8 and 7.0 +/- 0.6 pg/ml/10(3) M phi s, respectively) (p less than 0.01). However, M phi s from monkeys with AIDS failed to respond to LPS after 7 to 10 days in culture. In summary, in vitro infection with SIV does not cause constitutive TNF alpha release or alter the response of cultured M phi s to LPS. When kept in culture, M phi s collected from asymptomatic, SIV-infected animals retain their response to LPS, whereas M phi s from animals with AIDS lose the capacity to produce TNF alpha. Furthermore, M phi s cytokine production is exaggerated before overt clinical disease, but not as a direct result of infection with SIV.
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PMID:Effect of simian immunodeficiency virus infection on tumor necrosis factor-alpha production by alveolar macrophages. 189 Aug 5

The in vitro release of interleukin-1 beta (IL-1 beta) by peritoneal macrophages from CAPD patients was studied during 16 infection free periods (16 patients) and 13 episodes of peritonitis (10 patients) using an ELISA. Without exogeneous stimulation with LPS, peritoneal macrophages released the same amounts of IL-1 beta. irrespective if they were obtained during an infection free period (473 +/- 92 pg/ml 24h, means +/- SEM) or during peritonitis (324 +/- 125 pg/ml). However, in response to a dose of 5 micrograms/ml of LPS, peritoneal macrophages released significantly more (p less than 0.005) IL-1 beta during peritonitis (6155 +/- 1743 pg/ml). These findings show that during peritonitis, peritoneal macrophages are primed in vivo to release more IL-1 beta in vitro after stimulation with LPS, indicating that activation of peritoneal macrophages for IL-1 beta secretion occurs stepwise.
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PMID:Peritoneal macrophages from patients on CAPD show an increased capacity to secrete interleukin-1 beta during peritonitis. 198 87

Interleukin-1 (IL-1) release by peritoneal macrophages obtained from patients on continuous ambulatory peritoneal dialysis (CAPD) was studied in nine patients during an infection-free period and eight patients during an infectious peritonitis, using an ELISA for IL-1 beta. Without exogenous stimulation with LPS, peritoneal macrophages from infected and uninfected patients released the same amounts of IL-1 beta, 183 +/- 40 pg ml-1 24 h-1) per 10(6) cells (means +/- SEM) and 251 +/- 96 pg ml-1, respectively. However, in response to a dose of 5 micrograms ml-1 of LPS, peritoneal macrophages released significantly more (P less than 0.005) IL-1 beta during peritonitis (6579 +/- 2793 pg ml-1 24 h-1 per 10(6) cells) compared with the infection-free period (1040 +/- 182 pg ml-1). These findings show that after microbial invasion of the peritoneal cavity, peritoneal macrophages are primed in vivo to release an increased amount of IL-1 beta in vitro after subsequent exogenous stimulation with LPS, indicating that peritoneal macrophage activation for IL-1 beta secretion occurs in steps.
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PMID:Endotoxin-stimulated peritoneal macrophages obtained from continuous ambulatory peritoneal dialysis patients show an increased capacity to release interleukin-1 beta in vitro during infectious peritonitis. 212 5

The human monocyte-like cell line, U-937, is known to differentiate into macrophage-like cells following stimulation with phorbol myristate acetate (PMA) or interferon-gamma (IFN-gamma). The activated cells have been reported to have enhanced capacity to synthesize C2, C3, Factors B and H. Here, U-937 cells were used as a model system to investigate the effects of immunomodulatory agents on the biosynthesis of Factor P by monocytoid cells. Non-stimulated U-937 cells progressively secreted increasing amounts of Factor P over a 72-hr culture period. The secreted Factor P was hemolytically active. The daily production of Factor P was nearly linear (approx. 2.1 +/- 0.2 ng/10(6) cells; mean +/- SEM). Factor P synthesis was reversibly inhibited by cycloheximide indicating de novo synthesis. Both secreted Factor P and Factor P in normal plasma contained Factor P of heterogeneous molecular sizes and eluted from Sephacryl S-300 gel filtration column as a broad peak (mol. wt 250-800 kDa). The synthesis of Factor P by U-937 cells was augmented 1.8-, 2.1- and 2.5-fold respectively following induction with PMA (30 ng/ml), IFN-gamma (100 U/ml) and LPS (0.1 microgram/ml). Metabolic labeling of U-937 cells and autoradiograms of SDS-PAGE analysis of Factor P immunoprecipitates demonstrated a 54 kDa band in the culture supernate, co-migrating with purified 125I Factor P. Intracellular Factor P however had an apparent mol. wt that was 4000 kDa smaller than secreted Factor P. Thus U-937 cells synthesize a precursor Factor P subunit polypeptide chain which undergoes post-synthetic glycosylation and polymerization to give rise to the oligomers characteristic of native Factor P in fresh plasma. Our data also demonstrate that Factor P synthesis by monocytic cells can be enhanced by immunomodulatory factors or mediators that are generally found at sites of inflammation and immune response.
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PMID:Biosynthesis of complement factor P (properdin) by the human pre-monocyte cell line (U-937). 323 19

We attempt to elucidate the mechanisms of neutrophil (PMN) activation after burn injury. We previously reported prolonged elevations of PMN cell surface complement (C) opsonin receptor levels after burn trauma with a corresponding period of depressed PMN chemotaxis to C5a, which suggests that the C product, C5a, was responsible for PMN activation. However, a lack of direct correlation of C activation with C receptor levels soon after injury raised the possibility of a second PMN-activating substance. We therefore investigated the effect of endotoxin (LPS) on the expression of the C receptors (CR1 and CR3) by normal human PMNs. Concentrations from 0 to 50 ng/ml of LPS 026:B6 caused a dose response increase in the PMN surface expression of CR1 and CR3 as assessed by monoclonal antibody binding and indirect immunofluorescence. The relative CR1-dependent fluorescence rose from a mean of 50 to 385 and CR3 from 50 to 300. Chelation by ethylenediaminetetra acetic acid (EDTA) did not influence this dose response, thus ruling out the possibility of C activation by LPS--an inference supported by the lack of complement activation observed with these concentrations of LPS in normal serum. A similar dose response was obtained in the absence of other cell types or serum, which implies a direct effect that mimicked that of C5a. To determine the mechanism of the later, prolonged C activation after burn injury, we next examined C activation products in 22 patients with burn injuries. Elevations of plasma C3a desArg were present and persisted for 50 days. Elevations were at maximum levels on days 9 through 13 postburn (mean +/- standard error of mean [SEM], 496 +/- 47 ng/ml versus normal 113 +/- 32; p less than 0.01). These were accompanied by elevations of C4a desArg (917 +/- 154 ng/ml versus normal 424 +/- 50; p less than 0.01), which are indicative of classic pathway activation. Finally, we examined PMN function, phagocytosis and percentage killing of Staphylococcus aureus, and found PMN function to be unaltered in the 22 patients. Thus PMN activation after burn injury appears to be caused by LPS soon after injury and by C5a later after injury and affects only selected PMN functions.
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PMID:Neutrophil activation after burn injury: contributions of the classic complement pathway and of endotoxin. 330 5

Neonatal bacterial meningitis remains a life-threatening infection, and severe neurologic sequelae may be left in survivors as well. The goal of the study was to develop and characterize a porcine model of the disease with intravital observation of the permeability changes in cerebral microvessels. Eighteen newborn piglets were given doses of 0 ng (group 1), 20 ng (group 2), and 200 ng (group 3) of Escherichia coli 0111 B4 endotoxin (LPS) intracisternally (n = 6 in each group). Cardiovascular parameters were without changes, but a compensated metabolic acidosis occurred in group 3 4 h after LPS injection. Using the open cranial window technique combined with fluorescence excitation, there was no blood-brain barrier leakage in pial-arachnoid microvessels for sodium fluorescein during the 4 h of experiments in group 1 piglets, whereas spotty extravasations occurred in group 2 and in group 3 after the LPS injections (70.5 +/- 10.5 and 55.2 +/- 4.1 min, respectively, mean +/- SEM). A dose-dependent increase in sodium fluorescein uptake in brain regions examined (parietal and occipital cortex, cerebellum, and periventricular white matter) was also found by fluorescence spectrophotometry. LPS-treated piglets had developed pleocytosis. Four h after the challenge, the white blood cell counts in cerebrospinal fluid were (mean +/- SD): group 1, 8.2 +/- 7.6 microL-1; group 2, 453 +/- 703 microL-1; and group 3, 1 027 +/- 620 microL-1, respectively, whereas there was no change in white blood cell count of peripheral blood samples.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Escherichia coli 0111 B4 lipopolysaccharide given intracisternally induces blood-brain barrier opening during experimental neonatal meningitis in piglets. 823 23

Altered macrophage function after thermal injury is associated with increased production of PGE2 and TNF. However, it is not clear why synthesis of both cellular products remains elevated, as PGE2 is a potent inhibitor of TNF secretion. We studied the relationship between PGE2 and TNF synthesis in a murine model of thermal injury, and examined the effect of prostaglandin blockade on splenic macrophage secretion of these mediators of inflammation. LPS-stimulated production of PGE2 was significantly elevated in burn groups compared with sham-burned controls (pg/ml mean(SEM); sham 151(32): burn 597(147), p < 0.01). TNF production was similarly increased after thermal injury (pg/ml mean(SEM); sham 62(20): burn 928(316), p < 0.01). In vitro culture of macrophages with indomethacin augmented LPS stimulated TNF production in sham-burned controls but did not affect synthesis in burn groups, suggesting a loss of PGE2-dependent regulation of TNF synthesis after thermal injury. Direct measurement of TNF secretion as a function of exogenous PGE2 confirmed this dissociation between PGE2 and TNF synthesis, as burned animals displayed a 5-fold reduction in sensitivity to PGE2-induced inhibition of TNF, when compared with sham-burned controls (ID50 PGE2 molar; sham 1.26 x 10(-8): burn 6.43 x 10(-8), p < 0.05). In vivo pretreatment of burn groups with indomethacin for 5 days before assay partially restored sensitivity to the prostaglandin, and significantly down-regulated synthesis of both TNF and PGE2. These data show that thermal injury is associated with a loss of PGE2-dependent down-regulation of TNF synthesis, which accounts at least in part for increased TNF in these animals. In vivo cyclooxygenase blockade partially restored sensitivity to the prostaglandin and consequently down-regulated synthesis of TNF. These data further support existing evidence that suggests a potential therapeutic role for cyclooxygenase blockade after major thermal injury and trauma.
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PMID:Mechanism of increased tumor necrosis factor production after thermal injury. Altered sensitivity to PGE2 and immunomodulation with indomethacin. 834 98


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