Degree Granting Department
Mary E. Evans, Ph.D.
Shyam S. Mohapatra, Ph.D.
Immune, Cytokine, Lung, Tobacco, Pulmonary
Lung airway epithelium is the first line of defense against inhaled particulates such as cigarette smoke. Subepithelial dendritic cells (DC) survey the airway epithelial lining and represent the link between innate and adaptive immune response. No study has investigated the effect of cigarette smoke on DC in the presence of epithelial cells (EC). The purpose of this 4x2 factorial design study was to co-culture normal human bronchial epithelial (NHBE) cells with monocyte-derived dendritic cells (MDDC) and examine the effect of cigarette smoke condensate (CSC) and poly I:C stimulation (TLR3 ligand that mimics viral infection) on MDDC homotypic clustering, phagocytosis ability, surface marker expression, DC cytokine response, T cell (TC) proliferation and TC cytokine response. Experiments were performed with MDDC and TC derived from four individual donors.
Two planned comparisons (DMSO vehicle control compared to CSC high dose in both the no poly I:C and poly I:C stimulated groups) were analyzed. In MDDC stimulated with CSC, there was a significant increase in homotypic clustering, reduced phagocytosis, increased CD54, increased CD83 and CD86 maturation marker expression. Although no significant changes were observed in MDDC cytokine production, IL10 exhibited a trend to increase with CSC exposure but failed to reach statistical significance. Despite evidence that CSC exposed MDDC are maturing, there was no increase in TC proliferation; however in poly I:C stimulated co-cultures, CSC exposure increased IL2, IL5, IL10 and IL13 expression while non-stimulated co-cultures exhibited an increase in IL10 following CSC exposure.
This study indicates that cigarette smoke has the ability to decrease phagocytosis ability of DC and increases co-stimulatory maturation markers without inducing TC proliferation and potentiating a Th2 environment. These findings suggest that DC of smokers may be less likely to mount a normal immune response to invading pathogens thus providing evidence for smoker susceptibility to infection and how DC of smokers may respond to viral infection. In addition, these findings are particularly important in patients with allergic airway disease since increasing Th2 cytokines would increase the risk for disease exacerbation.
Scholar Commons Citation
Montpetit, Alison J., "Modulation of monocyte-derived dendritic cell maturation and function by cigarette smoke condensate in a bronchial epithelial cell co-culture model" (2008). Graduate Theses and Dissertations.