FUNCTIONAL EXPRESSION OF HUMAN AND MOUSE PLASMA PHOSPHOLIPID TRANSFERPROTEIN - EFFECT OF RECOMBINANT AND PLASMA PLTP ON HDL SUBSPECIES

The molecular cloning of mouse plasma phospholipid transfer protein (P LTP) and the eukaryotic cell expression of complementary DNA for mouse and human PLTP are described. Mouse PLTP was found to share 83% amino acid sequence identity with human PLTP. PLTP was produced in baby ham ster kidney cells. Conditioned medium from BHK cells expressing PLTP p ossessed both phospholipid transfer activity and high density lipoprot ein (HDL) conversion activity. PLTP mRNA was detected in all 16 human tissues examined by Northern blot analysis with the ovary, thymus, and placenta having the highest levels. PLTP mRNA was also examined in ei ght mouse tissues with the highest PLTP mRNA levels found in the lung, brain, and heart. The effect of purified human plasma-derived PLTP an d human recombinant PLTP (rPLTP) on the two human plasma HDL subspecie s Lp(A-I) and Lp(A-I/A-II) was evaluated. Plasma PLTP or rPLTP convert ed the two distinct size subspecies of Lp(A-I) into a larger species, an intermediate species, and a smaller species. Lp(A-I/A-II) particles containing multiple size subspecies were significantly altered by inc ubation with either plasma or rPLTP with the largest but less prominen t subspecies becoming the predominant one, and the smallest subspecies increasing in concentration. Thus, PLTP promoted the conversion of bo th Lp(A-I) and Lp(A-I/A-II) to populations of larger and smaller parti cles. Also, both human PLTP and mouse rPLTP were able to convert human or mouse HDL into larger and smaller particles. These observations su ggest that PLTP may play a key role in extracellular phospholipid tran sport and modulation of HDL particles.