On the fibrinolytic system in aged rats, and its reactivity to endotoxin and cytokines.

Aged rats are more susceptible to endotoxin-induced effects, including microthrombosis and platelet aggregation, than are young rats. To investigate whether changes in the fibrinolytic system might be involved, we investigated the fibrinolytic activity in plasma euglobulin fractions and tissues (lung and heart) of young (6-months old) and aged (24-months old) rats under baseline conditions and after challenge with endotoxin. Aged rats had lower plasma levels of tissue-type plasminogen activator (t-PA) and of urokinase-type PA (u-PA) activity.

Changes in endotoxin sensitivity in ageing. Absorption, elimination and mortality.

In this paper we describe the influence of ageing on responses to intravenously-injected endotoxin in two rat strains. Old age had no apparent effect on the absorption of 51Cr-labelled endotoxin from either jejunum or colon. Notwithstanding, aged animals appeared much more sensitive than their young counterparts to the lethal effects of intravenously injected endotoxin.

Comparative endotoxin-induced hepatic injury in young and aged rats.

Recent studies have demonstrated that aged rats are more susceptible to the lethal effects of endotoxin (ET) than young rats. The early (15 min to 7 h) hepatic ultrastructural and biochemical changes induced by ET in young (6 months) and aged (24 months) rats were evaluated to elucidate cell populations and/or the mechanisms that may be responsible for the previously observed differential effects. Aged rats given ET had significantly increased numbers of neutrophils in hepatic sinusoids at 30 min and thereafter as compared with ET-treated young rats.

Platelet participation in the increased severity of endotoxin-induced pulmonary injury in aged rats.

Recent studies have demonstrated that aged rats are more susceptible to the lethal effects of endotoxin as compared with young rats. The morphogenesis of early endotoxin-induced pulmonary injury in young (6 months) and aged (24 months) rats was examined by combined light and transmission electron microscopy to elucidate cell populations that may be responsible for these effects. Pulmonary endothelial cell injury was of greater severity and occurred at earlier time periods in aged rats as compared with young rats.

Isolation and culture of Kupffer cells from human liver. Ultrastructure, endocytosis and prostaglandin synthesis.

Kupffer cells and other sinusoidal cells were isolated after perfusion and incubation with pronase and collagenase of pieces of liver tissue obtained from organ donors. The resulting cell preparations contained endothelial cells, Kupffer cells and fat-storing cells as well as considerable numbers of leucocytes. Attempts to purify the different sinusoidal cell types by density centrifugation and centrifugal elutriation were successful only for Kupffer cells.

Cellular aging of the reticuloendothelial system.

The reticuloendothelial system (RES) consists of macrophages and other endocytic cells which contribute to natural resistance to disease agents. The RES has been implicated as being partly responsible for the observed age-related decrease in resistance to pathogenic microorganisms in man and experimental animals. It is largely unknown to what extent age-related deficiencies in specific functions of reticuloendothelial cells contribute to the decrease of RES functions.

Age-related changes in the endocytic capacity of rat liver Kupffer and endothelial cells.

There are many indications that the functional capacity of the reticuloendothelial system (RES) declines with age. The aim of this study was to investigate the cellular basis of age-related changes in the clearance function of the RES. The experiments were focused mainly on Kupffer and endothelial cells of the liver which represent a major part of the RES and are primarily responsible for clearance of colloidal material from the circulation.

Maintenance cultures of Kupffer cells isolated from rats of various ages: ultrastructure, enzyme cytochemistry, and endocytosis.

Sinusoidal liver cells were isolated from the livers of 3-, 12-, 30-, and 36-month-old female BN/BiRij rats by enzymatic digestion. The Kupffer cells in the sinusoidal cel suspensions were purified by centrifugal elutriation and kept in maintenance culture for periods of up to about 3 weeks. The viability and yield of Kupffer cells per gram of body weight did not change with the age of the donor rat.

Primary cultures of endothelial cells of the rat liver: a model for ultrastructural and functional studies.

A new isolation and purification procedure for endothelial cells of the rat liver and the conditions for large scale survival of these cells in maintenance culture are reported. Cells isolated by this new method and cultured with homologous rat serum on a collagen matrix show the restoration of several ultrastructural characteristics typical of rat liver endothelial cells in situ, including the broad cytoplasmic extensions that contain the sieve plates. These fenestrated cytoplasmic projections, which cover the liver sinusoids in vivo, are well preserved and are reformed in a manner reminiscent of the situation in situ.