Variant antigens and endothelial receptor adhesion in Plasmodium falciparum.

Parasite-derived proteins expressed on the surface of erythrocytes infected with Plasmodium falciparum are important virulence factors, since they mediate binding of infected cells to diverse receptors on vascular endothelium and are targets of a protective immune response. They are difficult to study because they undergo rapid clonal antigenic variation in vitro, which precludes the derivation of phenotypically homogeneous cultures. Here we have utilized sequence-specific proteases to dissect the role of defined antigenic variants in binding to particular receptors. By selection of protease-resistant subpopulations of parasites on defined receptors we (i) confirm the high rate of antigenic variation in vitro; (ii) demonstrate that a single infected erythrocyte can bind to intercellular adhesion molecule 1, CD36, and thrombospondin; (iii) show that binding to intercellular adhesion molecule 1 and CD36 are functions of the variant antigen; and (iv) suggest that binding to thrombospondin may be mediated by other components of the infected erythrocyte surface.

Characteristics of 86Rb+ transport in human erythrocytes infected with Plasmodium falciparum.

Human red cells infected in vitro with Plasmodium falciparum showed a significant increase in the rate of both ouabain-sensitive and ouabain-insensitive 86Rb+ influx. The increase in ouabain-insensitive 86Rb+ influx was due, in part, to increased transport via a bumetanide-sensitive system and, in part to transport via a pathway that was absent (or at least inactive) in uninfected cells. The parasite-induced pathway was inhibited by piperine and had a dose response very similar to that of the Gardos channel of uninfected cells but was less sensitive than the Gardos channel to inhibition by quinine.

Maternal and fetal metabolic effects of prolonged ritodrine infusion.

To investigate metabolic and endocrine changes in the fetus during prolonged maternal tocolysis with beta sympathomimetic drugs, ritodrine hydrochloride (2.1 micrograms/kg per minute) was infused into pregnant sheep near term. Confirming earlier studies, maternal plasma metabolite and hormone levels changed greatly during the first six to eight hours of infusion. Changes in the fetus paralleled these closely: glucose, lactate, and insulin increased sharply, but glucagon and alpha-amino acid nitrogen decreased. After this, most maternal and fetal plasma metabolite and hormone levels returned to the normal range and were unchanged by infusion for 72 to 96 hours. Fetal lactate levels, however, remained elevated. Similar changes occurred during interrupted maternal infusions of ritodrine. Prolonged infusion of ritodrine leads to diminished responsiveness in beta-adrenergic mechanisms regulating maternal plasma metabolite and hormone levels. Comparable unresponsiveness of fetal beta-adrenergic mechanisms, though less certain, could increase hazards during delivery and adaptation to postnatal life.

Glucagon and insulin release in the lamb before and after birth: effects of amino acids in vitro and in vivo.

The amino acids glycine, L-serine, L-asparagine and L-glutamine at 5 mmol/l each markedly increased glucagon release from perifused fetal lamb pancreas tissue, whereas the branched-chain amino acids L-leucine and L-valine had no effect. In contrast, only L-leucine and L-valine had any effect on insulin release. With perifused pancreas tissue from newborn lambs (5-9 days of age) glycine, L-serine, L-asparagine, L-arginine and L-lysine caused a similar marked increase in glucagon secretion with glycine having the greatest effect. These stimulatory effects were attenuated little by addition of glucose (20 mmol/l). L-Leucine had little effect on glucagon release, but was the only amino acid tested which caused marked insulin release in the absence of glucagon. Continuous intravenous infusion of glutamine (3 mmol/h per kg estimated fetal weight) or glutamine and asparagine each at this rate for 2 h into chronically cannulated fetal sheep in utero significantly increased plasma glucagon (P less than 0.05) and insulin (P less than 0.01) concentrations, although the effect on glucagon was not great. The results show how a range of amino acids can influence glucagon and insulin release from the pancreas of fetal and newborn lambs suggesting that physiological changes in plasma amino acid concentrations may contribute to regulation of glucagon and insulin release in utero in this species.