Defective monocyte chemotactic responses in diabetes mellitus

A variety of polymorphonuclear leukocyte (PMN) defects has been described in diabetics, but to date no investigations of monocyte (MN) function have been reported in diabetics. In the present studies, we have employed an underagarose chemotactic assay to examine directed and random motility of MNs from diabetic individuals. Among 45 diabetics and 25 controls there was no significant difference in the maximal distance migrated by the leading front of cells to zymosan-activated serum (chemotaxis) or medium alone (random migration). In contrast, many fewer diabetic MNs [293±28 (SE)] moved toward the attractant than did control MNs (446±21;P<0.001). Random motility of the diabetic MNs (121±14 SE) was also decreased compared to that of the controls (225±24;P<0.0004).In vitro incubation of the diabetic monocytes with insulin (25, 75, and 100 µU/ml) failed to improve chemotactic function. Treatment of diabetic MNs with 2,3-dihydroxybenzoic acid, a scavenger of H₂O₂ and O ₂ ^? , increased both random motility and directed movement, however. In addition,in vivo therapy of 7 diabetic patients with α-tocopherol (vitamin E) resulted in a marked increase in the number of MNs moving toward the chemoattractant (pretherapy, 118±12; posttherapy, 246±31;P<0.05). These results indicate that diabetic individuals have defective monocyte chemotactic function which can be corrected, in part, byin vitro orin vivo treatment with antioxidants. Thus, defective function may be, at least partly, the result of autooxidative membrane damage.