Direct effects of endotoxin on hepatocytes. Synthesis of a specific secretory protein

The synthesis of acute-phase proteins by the liver during sepsis has been thought to be induced primarily by monokines released from activated macrophages, although glucocorticoid hormones may also stimulate this process to a lesser degree. According to this concept, synthesis of these proteins following administration of bacterial endotoxins would be an indirect effect and would not reflect a direct interaction of the endotoxin molecule with the hepatic parenchymal cell. We observed, however, that the synthesis of a 23-kilodalton protein was stimulated directly by the addition of lipopolysaccharide to cultures of primary mouse hepatocytes. The synthesis of this protein was also stimulated by glucocorticoids and interleukin 1. These findings demonstrate that certain hepatic proteins are subject to complex regulation by several factors thought to be important mediators of sepsis; in addition, they suggest that hepatic parenchymal cells may have the intrinsic capacity to respond directly to bacterial endotoxins.     

Effect of interleukin 2 on Kupffer cell activation. Interleukin 2 primes and activates Kupffer cells to suppress hepatocyte protein synthesis in vitro

Interleukin 2 (IL-2) is an essential mediator of the immune response and has also been shown to be protective in experimental models of sepsis. Macrophages have IL-2 receptors but their function is unknown. We investigated the effect of IL-2 on Kupffer cells, the fixed macrophages of the liver, using an in vitro rat hepatocyte-Kupffer cell coculture system. In this model, endotoxin (lipopolysaccharide) triggers Kupffer cells to induce suppression of hepatocyte protein synthesis. We found that pretreatment with 10 U/mL or more of IL-2 primed Kupffer cells, significantly reducing the concentration of lipopolysaccharide necessary to trigger Kupffer cell-mediated suppression of hepatocyte protein synthesis. Higher concentrations of IL-2 (greater than or equal to 1 x 10(4) U/mL) alone were capable of priming and triggering Kupffer cells to suppress hepatocyte protein synthesis. These data show that IL-2 increases Kupffer cell sensitivity to endotoxin, suggesting that IL-2 may play an important role in regulating macrophage responses to septic stimuli.     

The development of cellular polarity in transport epithelia.

From the above discussion, it can be seen that the establishment of epithelial polarity plays a critical role in mammalian development. Functional and structural transitions in the vectorial processes of epithelial tissues in the developing embryo accompany critical events during development. Pathophysiologic states may arise due to either genetic or acquired abnormalities of polarity. Immaturity of vectorial transport functions frequently accompany the onset of premature birth and result in abnormal function of transport epithelia. Further definition of the molecular mechanisms that lead to the establishment and maintenance of epithelial polarity, as well as the developmental sequence of vectorial transport functions in developing epithelia, will lead to better understanding and treatment of fundamental disease states in the fetus and newborn.     

Distribution and structure of identified tonic and phasic synapses between L-neurones in the locust ocellar tract.

The ultrastructures and distributions of the discrete anatomical synapses which constitute two distinct types of output connections made by individual ocellar L-neurons, L1-3, are described. Outputs to neurones L4-5 are excitatory and transmit tonically, whereas reciprocal connections among the three L1-3 neurones are inhibitory and incapable of transmission for longer than a few milliseconds. The tonically transmitting synapses are located in the lateral ocellar tract and are made between the axons of L1-3, which do not receive inputs, and short branches of L4-5, which make no outputs. Each excitatory connection is composed of a few hundred discrete anatomical synapses, each characterised by a bar-shaped presynaptic density which is 0.15-1.5 microns in length and associated with a large number of round synaptic vesicles. Two postsynaptic profiles are apposed to each presynaptic density. Associated with tonic synapses are abundant invaginations of the presynaptic membrane. Synapses of the reciprocal, inhibitory, phasic connections occur in the protocerebral arbors of L1-3, among numerous output synapses of these neurones. Each phasic connection is composed of a few tens of discrete anatomical synapses. Each bar-shaped presynaptic density is associated with two postsynaptic profiles, and is 0.1-1.0 microns long. Compared with the tonic, excitatory connection, there are fewer vesicles and fewer invaginations of the presynaptic membrane associated with each synapse.