Roles for neutrophils and monocytes in murine cytomegalovirus‐induced microvascular dysfunction (678.16)

Abstract

One of the first responses of the vasculature to cardiovascular disease (CVD) risk factors, such as hypercholesterolemia (HC), is endothelial dysfunction, characterized by impaired arteriolar dilation and venular inflammation and platelet recruitment. Pathogens have been implicated in CVD, and we have recently shown murine cytomegalovirus (mCMV), also impairs endothelium‐dependent vasodilation. Although mCMV did not significantly increase blood cell recruitment, mCMV extended the first wave of inflammation (neutrophils) due to HC. Here we used spinning disk intravital microscopy to determine the identity of these recruited leukocytes, and light intravital microscopy to determine if these leukocyte subpopulations contributed to arteriolar dysfunction in mCMV‐infected mice on normal diet (ND) or high cholesterol diet (HC). We demonstrated that mCMV shifted populations of adherent leukocytes in microvasculature of HC mice from predominantly neutrophils towards ~1:1 GR‐1+ monocytes:neutrophils. Depletion of neutrophils using an anti‐Ly‐6G Ab restored arteriolar vasodilation in the mCMV‐HC, but not mCMV‐ND mice. It was also effective at abrogating leukocyte and platelet adhesion. Depletion of GR‐1+ cells (neutrophils and monocytes) protected against the arteriolar dysfunction in both mCMV‐ND and mCMV‐HC mice. These results suggest that mCMV causes a phenotypic shift in the inflammatory leukocytes recruited to venules during HC towards a larger monocyte component, although neutrophils remain key players in the arteriolar dysfunction. Furthermore, our data implicate a role for inflammatory GR‐1+ monocytes in the arteriolar dysfunction associated with mCMV infection.Grant Funding Source: Supported by COBRE GM103433‐NIGMS & Malcolm Feist Cardiovascular Research Endowment Fellowship, LSU