Osmolyte strategy in human monocytes and macrophages: involvement of p38MAPK in hyperosmotic induction of betaine and myoinositol transporters

Abstract

Betaine and myoinositol are compatible organic osmolytes which are specifically 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 describes an osmolyte strategy in human peripheral blood monocytes and human peripheral blood-derived macrophages. Hyperosmotic (405 mOsm) exposure of monocytes and macrophages led to an upregulation of betaine/gamma-amino-n-butyric acid (GABA) transporter BGT-1 and sodium-dependent myoinositol transporter SMIT in mRNA levels within 6 to 12 h. Induction of BGT-1 and SMIT mRNA occurred regardless of whether hyperosmolarity was induced by addition of NaCl (50 mM) or raffinose (100 mM). Betaine (5 mM) inhibited upregulation of BGT-1 as well as SMIT mRNA. After hyperosmotic (405 mOsm) exposure uptake of betaine and myoinositol was increased up to 10-fold compared to normoosmotic conditions. Hypoosmotic exposure led to a rapid efflux of betaine and myoinositol. Treatment of cells with the pyridinyl imidazole SB 203580 (10 microM), a specific inhibitor of p38 MAP kinase, inhibited the hyperosmolarity-induced increase in BGT-1 and SMIT mRNA as well as betaine and myoinositol uptake by 45-70%. The data show that human peripheral blood monocytes and human peripheral blood-derived macrophages use betaine and myoinositol are compatible organic osmolytes when exposed to osmotic stress and that p38MAPK is involved in hyperosmolarity-induced upregulation of osmolyte transporters BGT-1 and SMIT.