Effect of lead microparticles introduced into the respiratory system of the sensitivity of mice to Pasteurella multocida infection via aerosol]

Lead microparticles, resulting from the pyrolysis of organic lead used as an anti-knock agent in gasoline, were introduced into the lungs of Mice, during a short single exposure. When 6 microgram of lead were retained in the lungs (mean value per Mouse), the phagocytic ability of the pulmonary alveolar macrophages harvested 6 and 18 hrs. later, was significantly reduced. It was observed, in the same conditions, that the resistance of Mice to experimental infection by aerosolized Pasteurella multocida, was significantly reduced. When 3 microgram of lead were retained in the lungs, there was no significant difference between control and intoxicated Mice.     

Kinetics of decrease and apparent transformation of fluorescence spectra of benzo(a)pyrene absorbed by living cells: case of lymphocytes and macrophages]

A home made microspectrofluorimeter is used in order to follow the decrease of fluorescence intensity of Benzo(a)Pyrene after its absorption by single living cells. The kinetics look to be a first order one; fluorescent metabolite can be detected when peritoneal macrophages of Mice are used but not with human periferic lymphocytes pretreated with mitogens.     

Enhancement of peritoneal macrophage activity by bovine gamma globulin in mice

Mice treated with bovine gamma globulins showed an increased resistance to Salmonella typhimurium infection. This phenomenon seems to be bound to an increase of peritoneal macrophage phagocytic activity, as shown by the method of chemiluminescence, in experiments performed on peritoneal macrophages from mice treated with bovine gamma globulin.     

Cytotoxicity of mouse peritoneal cells after alloimmunization]

CBA Mice were immunized by two intraperitoneal injections of 30 X 10(6) DBA/2 or C57BL/6 spleen cells at days--12 and--2. Peritoneal cell population was obtained at day zero by washing the peritoneal cavity of Mice. Adherent cells were then separated using a 2 hrs. incubation in "Falcon" plates followed by washing. This macrophage-rich peritoneal cell population was found nonspecifically cytotoxic against 51Cr labeled tumoral target cells: P815 X DBA/2 mastocytoma cells, EL4 X C57BL/L lymphoma cells and spontaneous lymphoma AKR cells (same H--2k as CBA). This adherent peritoneal cell cytoxicity was demonstrated after 24 hrs. incubation with the target cells. It was found in nonspecific combination as well as when using target cells syngeneic to the donor. These findings suggest that adherent peritoneal cell cytotoxicity could be at least partly due to macrophages and result from factor (s) released by sensitized lymphocytes in vivo in the same way as has been previously demonstrated in vitro.     

Iron deposits in the chronically inflamed central nervous system and contributes to neurodegeneration

Neurodegenerative disorders are characterized by the presence of inflammation in areas with neuronal cell death and a regional increase in iron that exceeds what occurs during normal aging. The inflammatory process accompanying the neuronal degeneration involves glial cells of the central nervous system (CNS) and monocytes of the circulation that migrate into the CNS while transforming into phagocytic macrophages. This review outlines the possible mechanisms responsible for deposition of iron in neurodegenerative disorders with a main emphasis on how iron-containing monocytes may migrate into the CNS, transform into macrophages, and die out subsequently to their phagocytosis of damaged and dying neuronal cells. The dying macrophages may in turn release their iron, which enters the pool of labile iron to catalytically promote formation of free-radical-mediated stress and oxidative damage to adjacent cells, including neurons. Healthy neurons may also chronically acquire iron from the extracellular space as another principle mechanism for oxidative stress-mediated damage. Pharmacological handling of monocyte migration into the CNS combined with chelators that neutralize the effects of extracellular iron occurring due to the release from dying macrophages as well as intraneuronal chelation may denote good possibilities for reducing the deleterious consequences of iron deposition in the CNS.     

Post-weaning differential housing and testosterone secretion in male mice

Summary The effect of different densities of animals per cage on basal testosterone secretion and its response to some stimuli was studied in prepuberal male mice. Mice housed with 110 or 55 cm² of floor space per animal showed the same basal serum testosterone and hCG-induced testosterone release. Likewise, in a second experiment, the same basal serum testosterone and a similar response to acute noise stress were found in mice housed at 132, 66 or 22 cm² of floor space per animal. These results suggest that post-weaning crowding did not affect Leydig cell function in male mice.     

Lysozyme activates Enterococcus faecium to induce necrotic cell death in macrophages

Enterococci are commensal organisms in the alimentary tract. However, they can cause a variety of life-threatening infections, especially in nosocomial settings. We hypothesized that induction of cell death might enable these facultative pathogenic bacteria to evade the innate immune response and to cause infections of their host. We demonstrate that E. faecium when exposed to lysozyme induces cell death in macrophages in vitro and in vivo. Flow cytometric analyses of J774A.1 macrophages infected with E. faecium revealed loss of cell membrane integrity indicated by uptake of propidium iodide and decrease of the inner mitochondrial transmembrane potential ΔΨ_m. Inhibition of caspases, treatment of macrophages with cytochalasin D, or rifampicin did not prevent cells from dying, suggesting cell death mechanisms that are independent of caspase activation, bacterial uptake, and intracellular bacterial replication. Characteristics of necrotic cell death were demonstrated by both lack of procaspase 3 activation and cell shrinkage, electron microscopy, and release of lactate dehydrogenase. Pretreatment of E. faecium with lysozyme and subsequently with broad spectrum protease considerably reduced cell death, suggesting that a bacterial surface protein is causative for cell death induction. Moreover, in a mouse peritonitis model we demonstrated that E. faecium induces cell death of peritoneal macrophages in vivo. Altogether, our results show that enterococci, under specific conditions such as exposure to lysozyme, induce necrotic cell death in macrophages, which might contribute to disseminated infections by these facultative pathogenic bacteria.     

Semi-synthesis and proposed structure of platelet-activating factor (P.A.F.): PAF-acether an alkyl ether analog of lysophosphatidylcholine]

We have studied the molecular structure of platelet-activating factor" (P.A.F.), a mediator of inflammation obtained from blood leukocytes, macrophages, and platelets themselves. We have semi-synthetized a substance that possesses all the known physicochemical and biological characteristics of P.A.F. from hog leukocytes. This was performed by successive methylation, hydrogenation, and acetylation of lysophosphatidylethanolamine plasmalogen. We therefore propose the following structure for P.A.F.: 1-0-alkyl-2-acetyl-glyceryl-3-phosphorylcholine. This molecular structure is not yet described among the numerous substances capable of inducing platelet aggregation and release.     

Suppression of intrinsic B-cell function in Dengue-infected mice.

Mice infected with Dengue virus show a depressed immune response to lipopolysaccharide (LPS), a helper T-cell-independent antigen, when LPS was administered on day 0, 6 and 12 post infection. Mice injected with inactivated virus failed to show immunosuppression.     

The effect of continuous exposure to low frequency electric fields on three generations of mice: a pilot study.

Mice were allowed to mate, gestate, deliver and rear their offspring for 3 successive generations while being continuously exposed to 60 Hz electric fields. Mice exposed to vertical electric fields exhibited decreased body weights at 35 days postpartum and increased mortality rates for 3 successive generations. Mice exposed to horizontal electric fields exhibited decreased body weights for 2 successive generations.     

Transfer and induction of delayed hypersensitivity to methylated bovine serum albumin in the absence of adjuvant]

Delayed hypersensitivity to methylated bovine serum albumin may be induced in Mice without adjuvant, by injecting the antigen either with sensitized T lymphocytes, or by injecting just the antigen in Mice preptreated with Cyclophosphamid.     

IL-18 in inflammatory and autoimmune disease

Inflammation serves as the first line of defense in response to tissue injury, guiding the immune system to ensure preservation of the host. The inflammatory response can be divided into a quick initial phase mediated mainly by innate immune cells including neutrophils and macrophages, followed by a late phase that is dominated by lymphocytes. Early in the new millennium, a key component of the inflammatory reaction was discovered with the identification of a number of cytosolic sensor proteins (Nod-like receptors) that assembled into a common structure, the ‘inflammasome’. This structure includes an enzyme, caspase-1, which upon activation cleaves pro-forms of cytokines leading to subsequent release of active IL-1 and IL-18. This review focuses on the role of IL-18 in inflammatory responses with emphasis on autoimmune diseases.     

Effects of diacetoxyscirpenol on experimental candidiasis of mice

A single injection of 4.5 mg/kg of diacetoxyscirpenol (a toxin synthesized by Fusarium) into Mice challenged by C. albicans, increases significantly the development of an experimental candidiasis. Suspensions of homogenized kidneys was spread on Sabouraud dextrose agar plates and the colonies of C. albicans were counted after 24 hrs incubation. The mean values were determined. Comparison of mean values calculated for kidneys from the Mice challenged with C. albicans and those challenged with C. albicans plus toxin gave highly significant results.     

The effect of continuous exposure to low frequency electric fields on three generations of mice: A pilot study

Summary Mice were allowed to mate, gestate, deliver and rear their offspring for 3 successive generations while being continuously exposed to 60 Hz electric fields. Mice exposed to vertical electric fields exhibited decreased body weights at 35 days postpartum and increased mortality, rates for 3 successive generations. Mice exposed to horizontal electric fields exhibited decreased body weights for 2 successive generations.Supported by grants from National Institute of Health, and the Veterans Administration. Research Service, No. 0865-01.Vibration measurements were performed by Dr.Daniel A. Driscoll, New York State Department of Environmental Conservation.     

Role of serum components in the binding and phagocytosis of oxidatively damaged erythrocytes by autologous mouse macrophages

To investigate the role of autologous serum components in the recognition of damaged cells by macrophages, we examined the binding and phagocytosis of damage oxidatively damaged red blood cells with Cu2+ and ascorbate (oxRBCs) by autologous resident mouse peritoneal macrophages. The binding of oxRBCs by macrophages was independent of the presence of serum. However, phagocytosis by macrophages increased with serum concentration, and macrophages showed little ingestion of oxRBCs in a serum-free medium. Macrophages neither bound nor appreciably ingested native RBCs (before oxidation) in either the absence or presence of autologous serum. Mouse macrophages ingested significantly more native as well as oxRBCs in the presence of heat-inactivated fetal calf serum than in the presence of heat-inactivated mouse serum. Pretreated oxRBCs with normal serum were rarely ingested by macrophages in a serum-free medium. Phagocytosis of oxRBCs was significantly inhibited by depletion of IgG or calcium from serum, by heat inactivation of complement, or by antiserum against mouse C3. These results demonstrate that serum components such as IgG, C3, and calcium are involved in phagocytosis of oxRBCs by autologous macrophages.     

Demonstration of nucleotide pyrophosphatase and phosphohydrolase activities in normal lymphocyte of Balb/c mice and absence of these activities in YC8 tumor cells and in lymphocytes of animals with YC8 lymphoma]

Saline extraction of tumor cells from YC8 lymphoma transplanted in Balb/c Mice, of lymphocytes from animals bearing this tumor and of lymphocytes from control animals, allowed us to show important hydrolytic activities towards UDP-[(14C)]-galactose and galactose-[(14C)]-1-phosphate in normal lymphocytes. These activities disappear in lymphocytes from Mice bearing this tumor and in tumor cells themselves.     

Functional inhibition of isolated pancreatic cells, new technic for the detection of macrophage cytotoxicity]

It is usually accepted that macrophages "activated" by lymphokines may be found cytotoxic against tumoral target cells but show no detectable cytotoxicity in in vitro tests using normal non tumoral cells as target cells. These data have been obtained mainly with the chromium-release test. The present paper describes a new test using normal isolated pancreatic cells as target cells and evaluating the effect of activated or non-activated macrophages on the insulin secretion response to glucose stimulation. The results show a striking decrease in this response following an 18-hr incubation of pancreatic islet cells with activated macrophages, as compared to that of the same cells incubated with control macrophages. This is clear evidence that activated macrophages may alter normal cells and suggests that their cytotoxic properties are not restricted to tumoral target cells.     

Action of Corynebacterium parvum on the activity of glycosidases and proteases of peritoneal macrophages in the mice]

Glycosidase and peptidase of non-treated Mouse peritoneal macrophages were characterized. The enzymatic activities of Corynebacterium parvum stimulated Mouse macrophages were compared to those of macrophages obtained from non-treated animals. All the enzymatic activities, but beta-C-galactosidase, were higher in stimulated Mouse macrophages.     

The effects of a heterologous antibody against a crude lipoprotein lipase fraction in mice]

The antigens contained in a crude lipoprotein-lipase fraction from the Rabbit adipose tissue have no effect on Mice, even after daily injections for several months. But they induce an immune reaction in Sheep, allowing one to produce several immune sera with a high physiological activity, without any specific barrier between Rabbit and Mouse. After total absorption of these immune sera by normal Rabbit serum, the remaining antibodies have an activity against esterasic lipoproteins. Small doses of these antibodies induce in Mice marked hyperplastic and degenerative reactions of the adipose tissue and an extensive lysis of the pancreas. A correlative high lymphocytic activation, producing B and T immunoblasts, is induced.     

Stimulation by isoprinosine of the antiviral effect of interferon]

With a single dose of interferon, isoprinosine greatly enhances the antiviral protection of Mice against the lethal effect of encephalomyocarditis virus (100 LD 50).