Actin polymerization to chemotactic stimulus in diabetic neutrophils
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Chemotaxis and phagocytosis are essential steps in bacterial killing by neutrophil polymorphonuclear leukocytes (PMN). Leukocyte defects have been implicated in the development of long-term complications of diabetes mellitus but the effects of high blood glucose on the cytoskeleton are not clear. Upon chemoattractant signaling actin monomers are polymerized to form F-actin with corresponding changes in the cytoskeleton and cellular shape, thus enabling cell mobility during neutrophil chemotaxis. In this study, we investigated the effect of chronic and acute hyperglycemia on actin polymerization in fMLP-stimulated PM. The aim of this study was to identify the effect of chronic and acute hyperglycemia on actin polymerization in fMLP-stimulated PM. Actin polymerization was determined by flow cytometry analysis of fluorescent cytoskeletal staining. A mouse model of type-1 diabetes, Akita mice was utilized in this study. Experiments on Akita, wild type (WT) PMN and WT PMN in hyperglycemic media revealed that fMLP stimuIation induced rapid actin polymerization that was maximal in 10 seconds in both Akita and WT neutrophils. However, the F-actin fluorescent response was significantly smaller in Akita PMN compared to WT PMN. Within 60 seconds F-actin content returned to baseline levels in both groups. Acute glucose challenge in WT PMN resulted in similarly diminished actin polymerization.These findings indicate that both chronic and acute hyperglycemia impairs chemotaxis in PMN. Impaired chemotaxis might contribute to leukocyte dysfunction and impaired innate immune defense in diabetes.
PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact firstname.lastname@example.org.Dissertation (MSD) --Boston University, Henry M. Goldman School of Dental Medicine, 2011 (Department of Periodontology and Oral Biology).Includes bibliographic references: leaves 61-67.
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