Janet S. Kerr

Oxidant injury of the extracellular matrix: Potential role in the pathogenesis of pulmonary emphysema

This paper reviews evidence supporting a role for oxidants in the pathogenesis of pulmonary emphysema. Recent studies have shown that connective tissue components are directly degraded by oxidantsin vitro. Exposure of animals to oxidant gases causes degradation of lung connective tissue and results in an emphysematous lesion in the lung several weeks after recovery. Oxidant injury is also associated with an influx of inflammatory cells which release proteolytic enzymes. It is proposed that the emphsematous lesion found after exposure to an oxidant gas is the result of two mechanisms causing degradation of lung connective tissue: direct cleavage by free radicals and enzymatic proteolysis. It is possible that oxidant injury to the extracellular matrix is involved in the pathogenesis of emphysema in humans since cigarette smoke contains an exceedingly high concentration of oxidants.

Neutrophil Response following Intratracheal Instillation of Collagen Peptides into Rat Lungs

Inflammatory lung diseases are associated with destruction of interstitial collagen and release of degraded collagen fragments into the lower respiratory tract. To determine whether degraded collagen might be one factor mediating the cellular influx, we measured polymorphonuclear leukocytes (PMN) in bronchoalveolar lavage fluid following intratracheal instillation of collagen peptides. The responses to collagenous peptides derived from collagen digested with bacterial collagenase and to the collagenous-like polytripeptide (proline-proline-glycine) were examined. Both types of collagen peptides were chemotactic for human PMN in vitro. Two days following instillation of 5 mg collagenous peptides, we observed a threefold increase in the percentage of PMN in lavage fluid with a maximum (fivefold) response on day 6. Since other chemoattractants produce a response within hours when instilled intratracheally, we postulated that the late neutrophil influx produced with collagen may be the result of production of a neutrophil chemoattractant by alveolar macrophages. Alveolar macrophages treated with collagenous or collagenous-like peptides released PMN chemotactic factors, and the time course of release of chemotactic activity by alveolar macrophages in vitro correlated with the in vivo finding of a 2-6-day delay in PMN accumulation in the lungs. These observations are consistent with the idea that collagen peptides may stimulate alveolar macrophages to produce chemotactic factors for neutrophils. This mechanism may play a role in the accumulation of phagocytic cells in the lung following injury.

Inadequacy of blood drawn by cardiac puncture as a source for respiratory gas measurements in turtle (Pseudemys scripta)

Abstract 1. 1. pO2 was higher and pCO2 was lower in blood drawn from the carotid artery when compared to blood obtained by cardiac puncture. 2. 2. A pH difference between the two sources was not found. 3. Elevating body temperature caused an increase in pO2 in both sources. 3. 4. The effect on CO2 was not consistent in the two sources. 4. 5. It was concluded that the use of ventricular blood samples as an estimate for interpreting control function in the turtle could be misleading.

Substrate, enzyme and coenzyme levels in male and female rats from 3 to 24 months of age

Abstract 1. 1. Experiments were carried out to determine liver and brain enzyme, coenzyme and substrate levels in male and female rats at 3–24 months of age. 2. 2. Results confirmed that few consistent patterns of change with age appear in the coenzymes, enzymes and substrates measured. 3. 3. Liver glutamic and malic dehydrogenases as well as aspartic and malic acid levels in the female were higher at most ages compared with the male, suggesting hormonal influences. 4. 4. Since all rats were maintained under standardized conditions, and only one strain of rat was used, the changes observed were due to age and/or sex rather than to diet, strain, and/or environmental factors.

Clq Content of Serum and Lung Lavage Fluid of Rats Exposed to Toxic Levels of Oxygen

We used a sensitive hemolytic assay to measure the level of C1q, a subcomponent of the first complement protein in the classic pathway, in bronchoalveolar lavage fluid and serum of rats exposed to air and hyperoxia. The serum level was 125 +/- 5 micrograms/ml and the lavage level was 41 +/- 17 ng/ml in rats breathing air. In rats exposed to acute oxygen toxicity (95% O2 for 66 hr), the serum level was at 107 +/- 10 micrograms/ml, but the level in lavage fluid increased to 2457 +/- 400 ng/ml (p less than 0.05 compared to air). Administration of the proline analogue cis-4-hydroxy-L-proline to air- and O2-exposed rats reduced the serum C1q level by 28% and 34%, respectively (both p less than 0.05), presumably by interfering with metabolism of the collagen-like sequence of C1q. The level of C1q in bronchoalveolar lavage fluid is a sensitive marker of acute lung injury.

Effect of heat acclimation (32°c) on rat liver and brain substrate levels

Abstract 1. 1. Experiments were carried out to determine liver and brain enzyme, coenzyme, substrate and lipid levels in 3-month-old female rats exposed to ambient temperatures of 25° C or 32° C for 35 days. Food and water intake was observed during the acclimation period. In two male rats voluntary physical activity was also recorded during control and heat acclimation at 32° C. 2. 2. Food intake and voluntary physical activity were significantly decreased and water intake was significantly increased in the heat-acclimated group. 3. 3. Liver glutamic dehydrogenase increased and lactic dehydrogenase decreased in the acclimated group. No other metabolic changes were observed. 4. 4. The tissue changes found in this study and reported by others may be secondary to changes in dietary and physical activity patterns rather than the direct result of heat exposure.

Liver tissue substrates in the hyperthermic rat

1. 1. Experiments were carried out to determine whether elevated body temperature (Tr) altered metabolic pathways. 2. 2. Liver tissue levels of citric, malic, glutamic and asparati acids were measured in two strains of 3-month-old male rats at approximately 37 and 42·5°C. 3. 3. Malic acid levels were higher at 42°C than at 37°C in both strains. 4. 4. Radioactive pyruvate labelled at either C-1 or C-2 was administered to evaluate the possible origin of the increased malate. 5. 5. The results were interpreted to indicate TCA cycle activity decreased relative to the pyruvate carboxylase reaction.