ENVIRONMENTAL INFLUENCE ON AGE-RELATED-CHANGES OF HUMAN LYMPHOCYTE MEMBRANE VISCOSITY USING SEVERE COMBINED IMMUNODEFICIENCY MICE AS AN IN-VIVO MODEL

Peripheral blood lymphocytes (PBL) of healthy elderly people show incr eased plasma membrane viscosity compared to young subjects, that inver sely correlates with lymphocyte proliferation after mitogen stimulatio n in vitro. Maintenance of a constant membrane viscosity, which is nec essary for proper cell function, is crucially dependent on the membran e lipid composition. The cellular lipid metabolism, and thus lymphocyt e function, may be subject to modulation by diet or drugs. To study th e susceptibility of membrane viscosity to environmental conditions, we established an in vivo model using severe combined immunodeficiency ( SCID) mice: human peripheral blood lymphocytes from healthy young and old subjects were engrafted for three days intraperitoneally into SCID mice to offer identical environmental conditions. First, we demonstra te that human lymphocytes can take up and utilize murine lipoproteins: engrafted human PBL can participate in the mouse lipid metabolism, an d an exchange of membrane lipids in vivo is, therefore, possible. Seco nd, plasma membrane viscosity was determined before and after engraftm ent: before engraftment, PBL from the elderly showed a significantly h igher membrane viscosity than that from young controls, but this diffe rence vanished during engraftment into SCID mice, wherein cells from b oth age groups exhibited nearly identical values. It was, therefore, c oncluded that lymphocyte membrane viscosity is influenced by environme ntal factors, and that the age related increase is, in principle, reve rsible. (C) 1998 Elsevier Science Inc.