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Biomedical subjects

J E Repine

Publications and source records attributed to J E Repine.

At least 199 records · Page 11Linked to original sources
PubMed1982

Granulocytes mediate acute edematous lung injury in rabbits and in isolated rabbit lungs perfused with phorbol myristate acetate: role of oxygen radicals.

Acute edematous lung injury is associated with a marked increase in the number of granulocytes in the alveoli and microvasculature of the lung. Phorbol myristate acetate (PMA) causes granulocytes to adhere, aggregate, and release oxygen radicals and granular enzymes. We found that intravenously injected PMA caused a protein-rich edema in lungs of control rabbits but not in granulocytopenic rabbits pretreated with nitrogen mustard. Specifically, control rabbits treated with PMA had higher lung weight to body weight ratios (6.4 +/- 1.0 X 10(-3)) and lung lavage albumin concentrations (190 +/- 44 mg/dl) than granulocytopenic rabbits pretreated with nitrogen mustard and then given PMA (4.74 +/- 0.23 X 10(-3) and 9.9 +/- 3.8 mg/dl, respectively). To further clarify the role of granulocytes in the production of edema, additional experiments were conducted in an isolated perfused rabbit lung. Addition of purified granulocytes and PMA to the balanced salt perfusate caused lung edema, whereas neither granulocytes nor PMA alone caused edema. Specifically, increases in lung weights (42 +/- 9.2 g) and albumin concentrations (1,182 +/- mg/dl) in lung lavages from isolated lungs exposed to granulocytes and PMA were greater than increases in lung weights or albumin concentrations in lung lavages from isolated lungs exposed to granulocytes alone (2.0 +/- 0.4 g and 15 +/- 0.6 mg/dl), or to PMA alone (6.0 +/- 0.6 g and 81 +/- 34 mg/dl). To determine the contribution of oxygen radicals to the pathogenesis of the edema, chronic granulomatous disease granulocytes, which are deficient in oxygen radical production, were added to the isolated lung perfusate. Chronic granulomatous disease granulocytes and PMA did not cause edema in isolated lungs (delta lung weight 1.0 +/- 0.2 g and lavage albumin 12 +/- 5.0 mg/dl) whereas granulocytes from normal human subjects and PMA did (delta lung weight 43 +/- 5.2 g and lavage albumin 1,120 +/- 54 mg/dl). These data suggest that oxygen radicals released from stimulated granulocytes contribute to the pathogenesis of acute edematous lung injury.

Agranulocytosis↗
PubMed1982

Oxygen-radical-mediated permeability edema and vasoconstriction in isolated perfused rabbit lungs.

Oxygen radicals have been implicated in the pathogenesis of permeability pulmonary edema. To determine directly if O2 radicals can cause increased alveolar-capillary membrane (ACM) permeability and low-pressure permeability edema, we chemically produced O2 radicals in the sale perfusates of isolated rabbit lungs. The O2 radicals generated by xanthine oxidase caused protein-rich edema and increases in lung perfusion pressures that were inhibitable by catalase (hydrogen peroxide scavenger) or dimethylthiourea (hydroxyl radical scavenger) but not by superoxide dismutase. To determine the effect of O2 radicals on ACM permeability without interference from increased perfusion pressures, we used papaverine to maintain baseline perfusion pressures during O2 radical exposure and then assessed ACM integrity by evaluating the response of isolated lungs to elevated outflow pressures (10 mmHg for 10 min). Under these conditions, increased ACM permeability manifested by weight gains and lavage albumin accumulations occurred in lungs treated with xanthine oxidase but not in control lungs. We conclude that O2 radicals can cause increased ACM permeability and vasoconstriction in isolated lungs.

Animals↗
PubMed1982

Filtration deformability of rabbit pulmonary macrophage.

Rabbit PAM deformability was evaluated by positive-pressure filtration through Nucleopore membranes of well-specified pore diameter. The PAM filtration method was standardized and was influenced by apparatus variations (pore size, flow rate, cell concentration), environment (temperature, pH, divalent cations, protein concentration), and differences in PAM cell volume. The influence of phagocyte function on filtration deformability was evaluated by exposing PAMs to pharmacologic and physiologic agents with somewhat exclusive influences on phagocyte physiology. Agents that interact with microfilament contractile protein (N-ethylmaleimide, cytochalasin B) altered deformability profoundly, but no effect was observed with agents interacting with microtubules (vinblastine, colchicine). Agents that cause general PAM activation (phorbol myristate acetate) or stimulate chemotaxis (F-Met-Leu-Phe) increased deformability. On the contrary, PAM deformability was not changed by phagocytosis of Staphylococcus aureus or latex beads. Pharmacologic agents that alter PAM adhesion (aspirin, indomethacin, physiologic dose hydrocortisone) or inhibit glycolysis (2-deoxyglucose) had no influence on filtration deformability. Filtration PAM deformability reflects passive whole cell rigidity, which appears to be determined by the state of polymerization of the actin-myosin microfilament complex.

Animals↗
PubMed1981

Hydrogen peroxide kills Staphylococcus aureus by reacting with staphylococcal iron to form hydroxyl radical.

Two lines of investigation supported the premise that killing of Staphylococcus aureus, 502A, by hydrogen peroxide involves formation of the more toxic hydroxyl radical (.OH) through the iron-dependent Fenton reaction. First, growing S. aureus overnight in broth media with increasing concentrations of iron increased their content of iron and dramatically enhanced their subsequent susceptibility to killing by H2O2. Second, in direct relation to their effectiveness as .OH scavengers, thiourea, dimethyl thiourea, sodium benzoate, and dimethyl sulfoxide inhibited H2O2-mediated killing of S. aureus.

Free Radicals↗
PubMed1981

Dimethyl sulfoxide prevents DNA nicking mediated by ionizing radiation or iron/hydrogen peroxide-generated hydroxyl radical.

Eighty percent of the single-strand DNA breaks induced by gamma-irradiation were prevented by the hydroxyl radical (.OH) scavenger dimethyl sulfoxide (Me2SO); CH4 was generated in the process as a product of the interaction of .OH and Me2SO. In contrast, Me2SO completely blocked DNA nicking by an iron/H2O2 system which produces .OH but smaller amounts of CH4 from Me2SO. Because Me2SO prevented DNA breaks from the more efficient iron/H2O2 system but only blocked 80% of irradiation-mediated nicking, the results suggest that .OH is responsible for 80% of the DNA single-strand breaks and the remaining 20% is due to interactions not involving .OH.

DNA, Single-Stranded↗
PubMed1981

Altered oxidative metabolic responses in vitro of alveolar macrophages from asymptomatic cigarette smokers.

Superoxide anion (O2) release by alveolar macrophages (AM) from young asymptomatic cigarette smokers was greater than that by AM from age-matched nonsmokers. Greater O2 release by AM from cigarette smokers was observed before and after stimulation by bacteria or phorbol myristate acetate (PMA). In contrast, oxygen uptake and glucose (1(-14)C) oxidation by unstimulated or stimulated AM from cigarette smokers was the same as that by AM from non-smokers. The selective increase of O2 release by AM from cigarette smokers was not due to a lack of O2 scavenging agent within the cells, since intracellular superoxide dismutase (SOD) was increased in AM from smokers. The potential importance of enhanced O2 release by AM from cigarette smokers was confirmed by demonstrating that lysis of fibroblasts induced by AM from smokers was completely prevented by addition of SOD and catalase.

Adult↗
PubMed1981

Pulmonary inflammation due to oxygen toxicity: involvement of chemotactic factors and polymorphonuclear leukocytes.

Although the pathogenesis of pulmonary oxygen toxicity is not fully understood, the fact that increased numbers of polymorphonuclear leukocytes (PMN) are found in the lung and that these increases coincide with the massive endothelial damage raises the possibility that PMN may contribute to lung injury caused by hyperoxia. In order to begin to elucidate a mechanism for this influx of PMN, we measured the chemoattractant activity for PMN of lung lavages of rats exposed to greater than 95% oxygen for various durations. We found that the chemoattractant activity of the lavages of the lungs of rats exposed to hyperoxia for 66 h was markedly increased (9.66 +/- 1.0 times greater) compared with activities in lavages of normoxic control rats. Furthermore, these increases in chemoattractant activity in lung lavages correlated well with increases in the number of PMN (7 times greater than that in normoxic control animals) in the alveolar lavages that occurred after the rats had been exposed to hyperoxia for 66 h. These increases were followed in a few hours by the death of most of the rats (71%). These findings suggested that a close temporal relationship exists between the generation of high concentrations of chemoattractants in lung lavages, PMN influx into lung lavages, and death of rats exposed to hyperoxia. The results supported the possibility that PMN may be involved in the pathogenesis of pulmonary oxygen toxicity.

Animals↗
PubMed1981

Serum from patients with invasive fungal infections inhibits the adherence of polymorphonuclear leukocytes and alveolar macrophages.

Adherence of various combinations of polymorphonuclear leukocytes (PMN) or alveolar macrophages (AM) and serum from nonimmunosuppressed patients wit culture-proved, invasive fungal infections or control subjects was evaluated in vitro using the standard nylon fiber pipette technique. In autologous serum, adherence of PMN from patients with wide variety of untreated fungal infections, including blastomycosis, histoplasmosis, cryptococcosis, coccidiodomycosis, and spirotrichosis, was significantly (p less than 0.001) decreased when compared with PMN from uninfected control subjects or patients with untreated bacterial infections. Studies using various combinations of PMN and serums from patients with blastomycosis suggested that the adherence defect was due to a serum disorder rather than an intrinsic cellular abnormality. Preincubation in serum from patients with blastomycosis decreased the adherence of control PMN. Preincubation in control serum corrected the decreased adherence of PMN from patients with blastomycosis. Additional studies revealed that the inhibitor was heat-stable and reversible, being present before, but not after, treatment or spontaneous resolution of the patient's infections. Adherence of AM from patients with fungal infection was also normal except when AM were preincubated in serum from patients with untreated fungal infections. We concluded that the intrinsic adherence of PMN and AM from patients with untreated fungal infections is normal, but that these patients do have an extrinsic heat-labile serum factor that can decrease the adherence of PMN and AM.

Bacterial Infections↗
PubMed1981

Angiotensin converting enzyme concentrations in the lung lavage of normal rabbits and rabbits treated with nitrogen mustard exposed to hyperoxia.

Increased concentrations of angiotensin converting enzyme (ACE) were found in lung lavages from rabbits exposed to hyperoxia for 72 h and the concentrations of ACE were correlated with ratios of extravascular lung water to body weight (r = 0.69, p less than 0.05) and albumin concentrations in lung lavages (r = 0.89, p less than 0.01). In parallel studies, rabbits treated with nitrogen mustard in which granulocytopenia was maintained throughout the 72-h hyperoxic exposure period had less evidence of edematous lung injury and lower concentrations of ACE in their lung lavages than similarly treated rabbits in which granulocytopenia was not maintained. The results suggested that granulocytes contribute to acute edematous lung injury from hyperoxia and that ACE concentrations in lung lavages reflect this process.

Agranulocytosis↗
PubMed1981

Platelets increase neutrophil adherence in vitro to nylon fiber.

The effect of platelets on the adherence of neutrophils to nylon fiber was assessed in whole blood samples and purified neutrophil suspensions in the presence or absence of plasma. In whole blood samples, increasing numbers of platelets were associated (r = 0.47, p less than 0.02) with increasing adherence of neutrophils. Addition of platelets in plasma to purified neutrophil suspensions increased (p less than 0.05) neutrophil adherence from 76.2% +/- 1.4 to 88.0% +/- 2.0. Similarly, addition of washed platelets without plasma also increased (p less than 0.05) neutrophil adherence from 67.9% +/- 5.8 (without added platelets) to 94.2% +/- 1.6 (with 300,000 platelets/mm3 added). In contrast, no augmentation of neutrophil adherence occurred if platelets had their aggregation response suppressed by pretreating platelet donors with aspirin. SEM supported these findings by showing platelets in close association with neutrophils adhering to nylon fiber. These findings emphasize the importance of platelet numbers and reactivity on the adherence of neutrophils.

Aspirin↗
PubMed1980

Bactericidal function of neutrophils from patients with acute bacterial infections and from diabetics.

Killing of Staphylococus aureus by neutrophils from untreated patients with acute bacterial infection was increased compared with neutrophils from uninfected controls or the same patients after antibiotic treatment. In contrast, neutrophils from diabetics failed to increase their bactericidal activity in response to infection to the same degree as neutrophils from nondiabetic subjects. The latter abnormality was pronounced in poorly controlled (plasma glucose level, greater than 130 mg/100 ml), but was also present in well-controlled (plasma glucose levels, less than 130 mg/100 ml), diabetics. In parallel studies neutrophils from poorly controlled, uninfected diabetics did not kill S. aureus to the same degree as neutrophils from normal subjects or controlled diabetics. Finally, neutrophils from two diabetics who underwent controlled insulin withdrawal developed a bactericidal defect that was corrected by treating the patients with insulin or by preincubating their neutrophils with insulin in vitro. These results support the possibility that defective neutrophil bactericidal activity may contribute to the proposed increased susceptibility to bacterial infection of diabetics.

Acute Disease↗
PubMed1980

Phagocytosis by human alveolar macrophages and neutrophils: qualitative differences in the opsonic requirements for uptake of Staphylococcus aureus and Streptococcus pneumoniae in vitro.

The opsonic requirements for uptake of 3H-adenine-labeled Staphylococcus aureus (strains 502A, Wood 46, or 209) or Streptococcus pneumoniae (Type VII) by human alveolar macrophages (AM) or neutrophils (PMN) were evaluated and compared using a quantitative assay of phagocytosis. AM readily engulfed S. aureus organisms preopsonized with 1% albumin, serum, or serum that had been heated (56 degrees C for 30 min) to inactivate complement, whereas uptake of S. aureus by PMN occurred only after preopsonization with unheated, complement replete serum (2.5%). In contrast, uptake of S. pneumoniae organisms by AM or PMN did not occur with only albumin preopsonization, but required high concentrations (more than 40%) of unheated serum. The results indicate that there are qualitative and quantitative differences in the requirements for optimal ingestion of bacteria by human AM or PMN that relate not only to the type of organism but also to the type of phagocyte. Variations in opsonic requirements may be a key factor in the different cellular responses and clearances of inhaled S. aureus or S. pneumoniae organisms by the lungs.

Adenine↗