Various structural components of biological membranes are asymmetrically localized in the two surfaces of the membrane bilayer. This asymmetry is absolute for membrane (glyco) proteins, but only a partial asymmetry has been observed for membrane phospholipids. In the red cell membrane, choline-phospholipids are localized mainly in the outer monolayer whereas aminophospholipids are distributed almost exclusively in the inner monolayer. Several evidences are now available to suggest that this distribution of membrane phospholipids in red cells is directly or indirectly maintained by the membrane-associated cytoskeleton (membrane skeleton). This belief is well supported by the previous as well as recent studies carried out in the authors laboratory. Previously, it has been shown that lipid-lipid interactions play no major role in maintaining the transmembrane phospholipid asymmetry in erythrocytes, and that the asymmetry is lost upon covalent crosslinking of the major membrane skeletal protein, spectrin. The recent data presented here further shows that degradation or denaturation of spectrin indices rapid transbilayer movement of membrane phospholipids in the cells which, in turn, leads to more random phospholipid distributions across the membrane. These studies taken together strongly suggest that the skeleton-membrane associations are the major determinants of the transmembrane phospholipid asymmetry in erythrocytes, and that the dissociation of the skeleton from the membrane bilayer probably results in generation of new reorientation sites for phospholipids in the membrane.

The membrane phospholipid organisation in the red cells of humans suffering from chronic myeloid leukaemia has been analysed using the amino-group labelling reagent trinitrobenzenesulphonic acid and the fluid-sensing fluorophore, Merocyanine 540. Unlike the normal human erythrocytes, trinitrobenzenesulphonic acid in intact chronic myeloid leukaemia erythrocytes modified about 30% phosphatidylserine, under controlled conditions. Also, the chronic myeloid laukaemia red cells, but not the normal cells, were found to bind the fluorescent dye Merocyanine 540. These results demonstrate that loss of the transmembrane phospholipid asymmetry in chronic myeloid leukaemia erythrocytes is accompanied by an enhancement in the outer surface fluidity and, therefore, suggest that the red cells membrane phase-state asymmetry originates probably from the asymmetric arrangements of phospholipids across the membrane bilayer.

Liposome-coupled lepromin was found to elicit a 3-week skin reaction in leprosy patients similar to that elicited by wholeMycobacterium leprae. The present study suggests that the presentation of antigens in a specific orientation is necessary for evoking delayed type hypersensitivity response in humans.

Suitability of anti-erythrocyte F_(ab’)2-bearing liposomes as vehicles for chloroquine in the treatment of chloroquine resistantPlasmodium berghei infections in mice has been examined. Free chloroquine or chloroquine encapsulated in antibody-free liposomes failed to show much effect on the resistant infections, but the same doses of this drug after being encapsulated in antibody-bearing liposomes exhibited a significant inhibitory effect on this infection. These results indicate that chloroquine delivery in antibody targeted liposomes may help in the successful treatment of the chloroquine resistant malarial infections.

Antileishmanial activity and organ distribution of the antifungal drug Amphotericin-B in free and liposomised form have been studied in Balb/c mice infected withLeishmania donovani. Results indicate that Amphotericin-B in the liposomised form is significantly more active than the free form. This increase in the activity is perhaps related to the reduced drug toxicity rather than the altered drug distribution at the site of infection.