Evidence of ex vivo and in vitro impaired neutrophil oxidative burst and phagocytic capacity in type 1 diabetes mellitus.
In this study neutrophil (PMN) oxidative burst activity was investigated ex vivo and in vitro in comparison to the PMN-phagocytic functions ingestion and bacterial killing in poorly-controlled type 1 diabetic patients. Luminol enhanced chemiluminescence in response to phorbolesters as a measure of oxidative burst was assessed in a parallel detecting microtiterplate luminometer in 40 poorly-controlled type 1 diabetic subjects. PMN ingestion was measured with [3H]thymidine-labelled Staphylococcus aureus in a kinetic radiometric assay. Microbicidal activity was determined by pure plate counting of surviving bacteria (colony forming units, cfu) after defined pmn challenge. PMNs of type 1 diabetic subjects showed a highly significant reduction of peak CL response in response to PMA compared to nondiabetic controls (P < 0.001) and PMN ingestion (51.8 +/- 4.6%) and bacterial killing (28.6 +/- 3.2%) were reduced as well (78.2 +/- 5.2% (IN) and 18.4 +/- 4.1% (BK), P < 0.01, respectively). The in vitro data displayed impaired PMN oxidative burst activity at glucose concentrations > or = 13.8 mmol/l whereas PMN IN and BK were significantly reduced at glucose levels > or = 27.75 mmol/l. In the control group there was a positive correlation of peak CL response and IN as well as BK (P < 0.05); in type 1 diabetic patients this was also true, but did not reach statistical significance. The data obtained in this study clearly demonstrated impaired PMN oxidative burst activity and markedly reduced ingestion and bacterial killing in type 1 diabetic patients ex vivo and in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Marhoffer
W
W
III. Med. Clinic and Policlinic, University of Giessen, Germany.
Stein
M
M
Schleinkofer
L
L
Federlin
K
K
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects; D010587:Phagocytosis; D012016:Reference Values; D013211:Staphylococcus aureus; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D001786:Blood Glucose; D014316:Tritium; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine