Neutrophil adhesive dysfunction in diabetes mellitus; the role of cellular and plasma factors.
We examined neutrophil adherence to bovine aortic endothelial cells in 26 patients with diabetes compared with age- and sex-matched controls. The adherence of chromium 51-labeled neutrophils from patients with diabetes in the basal state and after incubation with phorbol myristate acetate (PMA) but not N-formyl-methionyl-leucyl-phenylalanine (FMLP) was decreased significantly. A subset of 16 of 26 patients demonstrated highly significant decreases in basal adhesion. No significant correlation was found between defective adherence and metabolic control as assessed by plasma glucose level (range 44 to 508 mg/dl) and hemoglobin A1 level (range 7.7% to 17.1%) at the time of study. Plasma from patients with diabetes increased adherence of both diabetic and control neutrophils in the basal state. The adherence-augmenting factor in diabetic plasma was found to be nonfilterable and partially heat labile and to manifest the characteristics of a protein. The adhesive effects of diabetic plasma were mediated through alterations in endothelium rather than neutrophils. Diabetic neutrophil aggregation induced by PMA, FMLP, and calcium ionophore was normal in all patients examined, regardless of the aggregating agent used. Fibronectin release in the basal state and after stimulation with FMLP was found to be comparable in diabetic and control neutrophils. These studies demonstrated intrinsic adhesive dysfunction of diabetic neutrophils and a factor or factors in diabetic plasma that enhanced adherence to endothelium. These cellular and humoral factors may act together to prevent tissue emigration of neutrophils and may contribute to the pathogenesis and susceptibility of infection in diabetes.
Andersen
B
B
Department of Medicine, Cleveland Metropolitan General Hospital, OH 44109.
Goldsmith
G H
GH
Spagnuolo
P J
PJ
D000328:Adult; D000368:Aged; D000818:Animals; D002417:Cattle; D002448:Cell Adhesion; D002449:Cell Aggregation; D003920:Diabetes Mellitus / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism
D005353:Fibronectins