Diacylglycerol-mediated signaling of neutrophils in diabetics with or without periodontal disease
Date
2005
DOI
Authors
El-Jamous, Bassam
Version
OA Version
Citation
Abstract
Diacylglycerol (DAG), a physiological activator of protein kinase C (PKC), was found to be elevated in unstimulated peripheral blood neutrophils from patients with diabetes mellitus (DM) compared with cells from normal individuals. These cells also showed an enhanced and prolonged elevation of DAG in response to fMLP stimulation. The data demonstrated no statistically significant difference in DAG content between type l and type 2 diabetes. The metabolism of DAG by DAG kinase (DGK) to phosphatidic acid (PA) was shown to be unaffected in diabetic neutrophils; no significant changes were seen in DGK activity in diabetic PMN compared to those of healthy control. The relationship between periodontal status and DAG content in both resting and fMLP stimulated neutrophils from diabetic patients was evaluated. The data revealed that within the diabetic group, patients with severe periodontitis exhibit significantly higher DAG levels in both stimulated and unstimulated neutrophils compared to patients without chronic periodontitis or patients with mild and moderate chronic periodontitis. Advanced glycation end-products (AGE) are elevated in the sera of diabetic patients. AGE has been shown to modulate immune competent cell activities. Therefore, in this study, we also examined the effect of AGE on DAG content in normal (non-diabetic) neutrophils. Neutrophils were incubated with 1.0 mg/ml CML-OVA for l hr. A significant increase in DAG level of CML-OVA-stimulated cell compared to OVA-control was detected. The priming effect of AGE stimulation has increased DAG generation in healthy neutrophils to a level similar to that reached when these cells were stimulated with fMLP. It is interesting to notice that DAG content in CML-OVA stimulated healthy control PMN levels that of DAG generation in diabetic non-stimulated cells. Secondary activation of neutrophils by fMLP primed with AGE did not further increase DAG in normal neutrophils. The effect of high glucose on DAG content in normal neutrophils was also examined. Incubation of healthy control PMN with either 5mM (90mg/dl) or 25mM(400mg/dl) glucose concentration for l hour period of time did not affect DAG level significantly in both stimulated and unstimulated conditions. Primary of neutrophils may require prolonged exposure to hyperglycemia. We conclude that elevated DAG content in diabetic neutrophils may explain the previously found increase in membrane bound PKC, thereby priming the cell to a hyperactive phenotype. We suggest that priming of diabetic neutrophils through AGE and probably through prolonged hyperglycemic condition may play an important role in the increased tendency of destructive form of periodontitis in diabetics.
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Thesis (MSD)--Boston University, Henry M. Goldman School of Dental Medicine, 2005 (Periodontics).
Includes bibliographical references: leaves 74-98.
Thesis (MSD)--Boston University, Henry M. Goldman School of Dental Medicine, 2005 (Periodontics).
Includes bibliographical references: leaves 74-98.
License
This work is protected by copyright. Downloading is restricted to the BU community. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.