Functional role of CD44, a principal receptor of hyaluronan, and glycated albumin for differentiation of resting human monocytes isolated by counterflow centrifugal elutriation was investigated. Flow cytometric analysis revealed that amadori-modified glycated albumin induced expression of CD44 as well as macrophage scavenger receptors (MSRs) such as CD36 and CD68 on resting monocytes. Crosslinking of CD44 on monocytes also induced MSR expression. Furthermore, CD44 crosslinking and/or glycated albumin enhanced the uptake of oxidized-low density lipoprotein in monocytes and foam cell formation. Taken together, engagement of CD44 (e.g., hyaluronan) and glycated albumin induced the differentiation of resting monocytes into foam macrophages through the induction of MSRs, implying that CD44 could be involved in atherosclerotic lesions of those such as diabetic patients. (c) 2005 Elsevier Inc. All rights reserved.