OSMOLYTE STRATEGY IN HUMAN MONOCYTES AND MACROPHAGES - INVOLVEMENT OFP38(MAPK) IN HYPEROSMOTIC INDUCTION OF BETAINE AND MYOINOSITOL TRANSPORTERS

Betaine and myoinositol ape compatible organic osmolytes which are spe cifically accumulated by cells exposed to hyperosmotic medium. A role for compatible organic osmolytes in the regulation of immune function for rat liver macrophages has been described recently. This report des cribes an osmolyte strategy in human peripheral blood monocytes and hu man peripheral blood-derived macrophages. Hyperosmotic (405 mOsm) expo sure of monocytes and macrophages led to am upregulation of betaine/ga mma-amino-n-butyric acid (GABA) transporter BGT-1 and sodium-dependent myoinositol transporter SMIT in mRNA levels within 6 to 12 h. Inducti on of BGT-1 and SMIT mRNA occurred regardless of whether hyperosmolari ty was induced by addition of NaCl (50 mM) or raffinose (100 mM). Beta ine (5 mM) inhibited upregulation of BGT-1 as well as SMIT mRNA. After hyperosmotic (405 mOsm) exposure uptake of betaine and myoinositol wa s increased up to 10-fold compared to normoosmotic conditions. Hypoosm otic exposure led to a rapid efflux of betaine and myoinositol. Treatm ent of cells with the pyridinyl imidazole SE 203580 (10 mu M), a speci fic inhibitor of p38 MAP kinase, inhibited the hyperosmolarity-induced increase in BGT-1 and SMIT mRNA as well as betaine and mycoinositol u ptake by 45-70%. The data show that human peripheral blood monocytes a nd human peripheral blood-derived macrophages use betaine and myoinosi tol are compatible organic osmolytes when exposed to osmotic stress an d that p38(MAPK) is involved in hyperosmolarity-induced upregulation o f osmolyte transporters BGT-1 and SMIT. (C) 1998 Academic Press.