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L D Loose

Publications and source records attributed to L D Loose.

At least 37 records · Page 2Linked to original sources
PubMed1984

Biochemical and functional alterations in macrophages after thermal injury.

Biochemical and functional measurements of rat pulmonary alveolar macrophages were measured 4 h after 1 10-s, 26 to 28% total body surface area, full-thickness scald burn induced under ether anesthesia. Both phagocytic activity and capacity were significantly decreased to a comparable extent, whereas microbicidal activity was increased almost twofold in macrophages from the burned animals. Concurrent with the decreased phagocytic function was a marked impairment in chemotaxis and random migration of these cells when zymosan-activated serum was used as the chemoattractant. When biochemical parameters were examined, it was demonstrated that, on a per-cell but not total-protein basis, alveolar macrophages from burned animals had elevated levels of RNA, total protein beta-glucuronidase, acid phosphatase, and 5'-nucleotidase. These results raise the possibility that the increased pneumonitis in burned individuals may be due to more complex macrophage dysfunctions than impaired microbicidal activity, as was once thought. Alternatively, the biochemical and functional changes observed may be a reflection of a new population of macrophages appearing in the lungs after thermal injury.

5'-Nucleotidase↗
PubMed1983

Synthetic immunomodulators for prevention of fatal infections in a burned guinea pig model.

Individuals who have suffered severe trauma, such as burns, have a high incidence of infection associated with impaired host resistance. Nonspecific stimulators of host defense mechanisms, i.e., immunomodulators, may be of benefit in such situations. A small animal model (guinea pigs) was developed to study the efficacy of immunomodulators in burns. Anesthetized animals received a 20% total body surface area, full-thickness, scald burn. There was no mortality associated with this injury, but these animals were highly susceptible to challenge with Pseudomonas aeruginosa strain 1244 by direct injection into the burn wound within 24 hours of injury. This susceptibility persisted about 7 days. The standard model adopted was to injure animals, then challenge with 1 median lethal dose (LD50) of P. aeruginosa 96 hours after injury. Using this model, six synthetic immunomodulators were tested: CP-20,961, CP-46,665, muramyl dipeptide, thymopoietin pentapeptide (TP-5), levamisole, and lithium. Drug administration began 24 hours after injury and ended prior to challenge with P. aeruginosa at 96 hours. CP-20,961, muramyl dipeptide, levamisole, and lithium all had no beneficial effect on survival. A single dosage (0.3 mg/kg, I.V.) of CP-46,665, administered 24 hours postinjury, increased the survival rate from 50% to 85% and mean survival time (MST) from 8.2 days to 12.4 days. TP-5, given in four doses (0.1 mg/kg, I.V. each) every 24 hours, increased the survival rate from 40% to 80% and MST from 6.9 days to 11.6 days. These data show that immunomodulators could be of benefit in burns, but also that not all agents are effective in this particular situation.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1982

Macrophage induction of T-suppressor cells in pesticide-exposed and protozoan-infected mice.

The use of infectious pathogens has allowed the detection of the development of synergism between pathogens and ubiquitous environmental chemical contaminants. This synergism has been demonstrated to result in a state of immunosuppression which either did not occur in the independent and singular presence of the chemical or pathogen and/or was greater than additive when both were combined. The immunosuppression was distinct with regard to the organochloride used and, therefore, is not a ubiquitous characteristic of all organohalides. The production of a macrophage soluble factor which appeared to induce T-suppressor cells was demonstrated in hepatic Kupffer cells from mice administered 5 ppm of dieldrin for 10 weeks and then infected with Leishmania tropical promastigotes. The factor was not generated in mice administered dieldrin and infected with malaria nor in mice administered only dieldrin nor in mice only infected with Leishmania. Additional studies revealed a profound impairment in macrophage antigen processing with macrophages obtained from mice administered dieldrin. The use of pathogen models may allow the immunosuppressive potential of environmental chemical contaminants to be expressed in a more sensitive manner.

Animals↗
PubMed1981

Assessment of environmental contaminant-induced lymphocyte dysfunction.

Although it has been established that environmental contaminants can alter immune function, the mechanisms of action have yet to be determined. This paper reviews the effects of hydrocarbon environmental contaminants on lymphocyte function and presents an approach which may serve to delineate the mechanisms of action. The approach is based on the use of the developmental phases of an immune response and assays which can be used for their functional assessment. Possible interactions between environmental contaminants and lymphocyte function and factors which must be considered in the evaluation of immune status are discussed. In addition, a study on the influence of the chronic exposure to two polyhalogenated hydrocarbons, PCB and HCB, on several parameters of lymphocyte function in mice is presented.

Animals↗
PubMed1981

Environmental chemical-induced macrophage dysfunction.

Immunomodulation by environmental chemical contaminants and the role immune parameters play in toxicity and risk assessment studies is of increasing concern. Although considerable evidence has indicated that various xenobiotics may be immunosuppressive, little attention has been directed toward ascertaining a specific cellular locus which could be responsible for the impaired immune responsiveness. Since previous studies had suggested a macrophage defect in xenobiotic-induced immunosuppression and since macrophages are integral components of an immune response, an in-depth evaluation of macrophage function was conducted in xenobiotic-exposed mice. Macrophages isolated from mice receiving PCB, HCB, and dieldrin had no alteration in their in vitro O2 consumption while at rest or during phagocytosis. In addition, no alteration in in vitro phagocytic activity, phagocytic capacity or microbicidal activity was demonstrated. However, a significant impairment in the in vivo phagocytic clearance of a labelled antigen and an altered tissue distribution of the antigen was observed and was, perhaps, related, in part, to a significant decrease in serum fibronectin, an opsonic alpha 2 surface-binding glycoprotein. Furthermore, animals exposed to HCB and dieldrin, but not to PCB, had a profound decrease in their resistance to a challenge tumor cell implant which was related to a select alteration in tumor cell killing. The adherent spleen cells from HCB-treated mice had a profound suppression in their tumoricidal activity which was in contrast to dieldrin-treated mice, where the target cell type appeared to be the nonadherent cells. However, although dieldrin-exposed adherent cells (macrophages ?) did nt appear to have an altered tumoricidal capacity, all four macrophage types isolated from dieldrin-treated mice had a significantly impaired ability to process a cellular antigen. Splenic and alveolar macrophages appeared to be the most sensitive cell types to dieldrin. The present studies suggest that macrophage dysfunction may be an integral part of xenobiotic-induced immunosuppression and that the effector but not affector component of macrophage function may be the site of alteration.

Animals↗
PubMed1981

Corynebacterium parvum treatment of P388 tumor-bearing mice. I. Lysosomal enzyme levels in adherent peritoneal cells and peritoneal lavage fluid.

BDF1 mice treated with Corynebacterium parvum (C. parvum) 2 days before an implant of 106 P388 leukemic cells had up to an 110% increase in survival time above control; Bacillus Calmette-Guérin (BCG) treatment was ineffective. Acid phosphatase and beta-glucuronidase were measured in adherent peritoneal lavage cells and beta-glucuronidase in peritoneal lavage fluid form mice treated with C. parvum or BCG 2 days before the implant of P388 cells. In the presence of the tumor, adherent peritoneal cells from C. parvum-treated animals had a 250-300% increased specific lysosomal enzyme activity above control values (cells form animals receiving tumor implant alone). Peak enzyme activity which occurred on day 3 was not present in adherent cells from BCG-treated tumor-bearing animals or the control animals. The beta-glucuronidase activity in peritoneal lavage fluid was elevated by the tumor cells, BCG, or C. parvum. Peak levels occurred on day 5 regardless of the treatment with an additive effect present on day 5 in animals receiving the combination of tumor with C. parvum. The evidence indicated the development of a different pattern of enhanced lysosomal enzyme activity if the immunopotentiator protected against the P388 tumor vs one that did not. Protection was associated with an increase in lysosomal enzyme activity in adherent cells with no increase in lavage fluid in the presence of tumor cells. Changes in cellular enzyme activity may prove to be diagnostic for antitumor activity by an immunostimulant.

Acid Phosphatase↗
PubMed1981

Corynebacterium parvum treatment of P388 tumor-bearing mice. II. Lysosomal enzyme levels associated with P388 tumor cells.

The number of tumor cells recovered form the peritoneal cavity of mice administered Corynebacterium parvum (C. parvum), Bacillus Calmette-Guérin (BCG) or saline 2 days before tumor implant was assessed on days 1, 2, 3, 5 and 7 following the intraperitoneal (ip) administration of 10(6) P388 leukemic cells. C. parvum-treated mice manifested a significant decrease in the number of tumor cells recovered from the peritoneal cavity on days 3-7, while BCG-treated mice had tumor cell yields comparable to saline control values. Lysosomal enzyme activity (acid phosphatase and beta-glucuronidase) in the nonadherent lavage cell population, which comprised tumor cells and host cells obtained form tumor-bearing animals, closely reflected the changes observed in tumor cell numbers and was initially assumed to be associated with tumor cells. When lysosomal enzyme activity was expressed as a function of the number of tumor cells or cellular protein, an enhanced activity following C. parvum treatment but not following BCG treatment was demonstrated. Enzyme activity associated with tumor cells was maximal 2 days prior to the profound depression in tumor cell maximal 2 days prior to the profound depression in tumor cell yield and may be associated with tumor cell killing. It is concluded that a correlation may exist between lysosomal enzyme activity, tumor cell numbers and the protective effect of the immunostimulant C. parvum. Whether the correlation is direct or indirect remains to be resolved.

Acid Phosphatase↗
PubMed1981

Impaired mineral metabolism in postburn muscle.

Rats were scalded on one hind limb and sacrificed by exsanguination at 4 hours, 1 day, and 3 days postburn. Concentrations of sodium, potassium, calcium, magnesium, and phosphate were measured in serum and in calf muscles from the burned and unburned limb of burned rats and controls. At 4 hours postburn, the injured rats exhibited a 5.4% elevation in serum potassium, a 23% increase in serum magnesium, and a 15% rise in serum phosphate compared to controls. At 3 days postburn, serum calcium and phosphate levels of burned rats were 7 and 13%, respectively, below controls. Tissue electrolytes in calf muscles from the unburned limb of burned rats did not differ from controls. In contrast, calf muscles of the burned limb showed up to a 202% increase in sodium content and up to a 61% fall of potassium content; the tissue Na/K ratio was elevated more than threefold at all test times. Burned muscles' calcium content was increased 127% at 4 hours, 112% at 1 day, and 21% at 3 days postburn. Magnesium and phosphate contents did not differ from controls at 4 hours postburn, but gradually decreased 58 and 59%, respectively, during the observation period. The data suggest that muscles underlying the burned wound show increased cell permeability and/or impaired active ion transport. These alterations as well as the loss of magnesium and phosphate may be related, in part, to the previously demonstrated depletion of ATP and adenine nucleotides in thermally injured muscles.

Animals↗
PubMed1980

Depression of the respiratory burst in alveolar and peritoneal macrophages after thermal injury.

The resting O(2) consumption of alveolar and peritoneal macrophages obtained from rats at 4 and 24 h after thermal injury was unaltered from control values. However, when heat-killed Pseudomonas aeruginosa or polystyrene latex particles were added to the cell suspensions to initiate phagocytosis, a significant depression in the respiratory burst accompanying the phagocytic event was demonstrated. The addition of phorbol myristate acetate, used to maximize the respiratory response, was ineffective in elevating, to control values, the respiratory burst of macrophages obtained from burned animals. The deficit was only, in part, serum mediated since the responses could not be restored to control values even when the cells from the burned animals were vigorously washed with control serum and incubated with control serum. The contribution of a burn serum factor, which was non-dialyzable, heat stable at 56 degrees C but not at 65 degrees C, and insensitive to pronase treatment, must be considered. These data indicate that thermal injury results in macrophage metabolic alterations which are mediated, in part, by a burn serum factor. Furthermore, the data suggest that pulmonary alveolar macrophages are more sensitive to thermal injury than peritoneal macrophages. Serum factors contributed, in part, to this observed impairment in the respiratory burst as indicated by: (i) an approximate 50% reversal of the impairment by control serum, and (ii) an approximate decrease of 50 to 80% in the control alveolar macrophage respiratory burst when serum from the thermally injured rats was added to the culture medium.

Animals↗
PubMed1980

Optimal conditions for antitumor activity of C. parvum against the ascites form of sarcoma 180.

Single and multiple doses of Corynebacterium parvum (C. parvum) ranging from 0.1--60 mg/kg were tested for antitumor activity against 10(6) sarcoma 180 cells in male CD1 mice. Determinations were made of the optimal dose and time of treatment needed to produce maximum suppression of the tumor using both median survival time and percent survival to day 90 as endpoints. A dose of 1 mg/kg given 3 days before sarcoma 180 transplant produced complete protection (100% survival). All other treatment regimens produced less of an effect. Single doses of 1, 10 and 60 mg/kg had significant antitumor activity when administered either on day 3, 2, or 1 before tumor implant, 0.1 mg/kg protected only when given on day 3. All single doses given 5 or 8 days before and anytime after tumor were ineffective. Multiple doses were only of advantage over single doses when treatments were after tumor cell inoculation. In vitro cytotoxicity studies demonstrated that both 1 and 60 mg/kg enhanced tumor cell killing by cells isolated from the peritoneal cavity, with the 1 mg/kg dose producing a greater effect. It was concluded that dose and time of administration of C. parvum, in relation to tumor implant, were important in determining optimal antitumor activity against sarcoma 180.

Animals↗
PubMed1980

Dose-dependent macrophage stimulation by Corynebacterium parvum.

Corynebacterium parvum (C. parvum) administered at a dose of either 0.1, 1 or 10 mg/kg intraperitoneally (ip) to BDF1 mice was evaluated for its influence on peritoneal exudate cell differentials, numbers, respiration, phagocytic activity and capacity and intracellular microbicidal activity. The ip administration of 1 mg/kg of C. parvum resulted in a 2-3 fold increase in the yield of peritoneal exudate cells 1-5 days after injection; 0.1 mg/kg was ineffective, while 10 mg/kg of C. parvum manifested an increased cell yield on days 1 and 5 following injection. No alterations in cell differentials were noted at any dose level. A trend toward a dose-related alteration in the respiratory burst, phagocytic activity and capacity was demonstrated. The most dramatic alteration observed was a profound increase in intracellular microbicidal activity in macrophages obtained from mice administered 1 mg/kg of C. parvum. The higher dose of C. parvum was suppressive. It was concluded that a relationship between macrophage microbicidal activity and tumor cell killing exists because the 1 mg/kg, which elicited maximal macrophage microbicidal activity, also induced the greatest increase in protection against two unrelated tumor models as previously reported.

Animals↗
PubMed1979

Environmental chemical-induced modification of cell-mediated immune responses.

It is therefore proposed that: 1) environmental chemicals can have specific mechanisms of toxicity and can influence antibody-mediated immunity while having no detectable effect on cell-mediated immunity, 2) immune dysfunction is related to exposure time to a chemical and the tissue concentration of that chemical, 3) recovery of immune function may occur even though chemical exposure continues, and 4) a single assay of immune function may not be appropriate to detect chemical induced immune dysfunction.

Animals↗
PubMed1979

A rapid, inexpensive and easily quantified assay for phagocytosis and microbicidal activity of macrophages and neutrophils.

The objective of the present study was to develop a technique to quantitate the phagocytic and intracellular microbicidal activity in different populations of phagocytes, i.e. neutrophils and macrophages. Elicited peritoneal neutrophils and macrophages as well as alveolar macrophages and adherent splenic macrophages were used as representative cell types. The method to assess intracellular killing was based upon dye uptake and concentration by a dead micro-organism; methylene blue was used as the indicator dye and the test organism was Saccharomyces cerevisiae. Phagocytosis was measured by counting, microscopically, the number of ingested yeast (Saccharomyces cerevisiae) within the neutrophils or macrophages. A number of killed yeast, i.e., those which took up the dye, were readily visualized. The temporal pattern of phagocytosis and killing was determined concurrently. Splenic macrophages demonstrated the slowest phagocytic activity whereas neutrophils and alveolar macrophages manifested a similar phagocytic activity. Peritoneal macrophages exhibited a continuous increase in activity throughout the test period. Microbicidal activity was similar for all 4 cells types. The new technique for measuring phagocytosis and killing provides a rapid, inexpensive and easily quantified assay for assessing discrete phagocytic cell functions.

Animals↗
PubMed1979

Macrophage dysfunction after burn injury.

The phagocytic and microbicidal activities of alveolar and peritoneal macrophages were evaluated 4 and 24 h after a full-thickness scald burn of 26 to 28% body surface area in anesthetized rats. The contribution of serum factors to the macrophage functions was studied concurrently. The phagocytic activity of alveolar macrophages obtained 4 or 24 postburn was reduced approximately 65% below control values when they were incubated in media containing autologous serum and approximately 45% (below controls) when they were incubated in media containing normal (control) serum. A similar, although not as marked, decrease in the phagocytic activity of peritoneal macrophages was also demonstrated. Serum obtained from rats 4 or 24 h postburn had a significant suppressive effect on the phagocytic activity of control alveolar, but not peritoneal, macrophages. The intracellular microbicidal activity of peritoneal macrophages obtained at the postburn intervals and incubated in media containing either autologous or control serum was unaltered from control values. However, alveolar macrophages obtained 24 h, but not 4 h, postburn had a significant (approximately 80%) increase, above control values, in their microbicidal activity. Serum obtained 24 h, but not 4 h, postburn stimulated control alveolar macrophage killing ability. These data indicate that thermal injury induces a defect in the phagocytic activity rather than the microbicidal activity of macrophages. This phagocytic alteration is mediated, in part, by serum.

Animals↗