Browsing by Author "Johnston, William Brent"

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    Leukocyte recruitment mechanisms in acute and chronic inflammation
    (1999) Johnston, William Brent; Kubes, Paul
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    Recruitment of neutrophils to the lymph node and their role at steady state and after Staphylococcus aureus infection
    (2020-03-25) Bogoslowski, Ania; Kubes, Paul; Mody, Christopher; Ousman, Shalina; Finney, Constance; Johnston, William Brent
    The contribution of lymph nodes to the adaptive immune response is well studied. However, their function as an innate immune organ has been overlooked. In this thesis, neutrophils are identified in the lymph node at steady state. The entry of these neutrophils is entirely dependent upon L-selectin. After entering the lymph node, neutrophils at steady state will recirculate, exiting from the lymph node via efferent lymphatics in an S1P-dependent manner. In mice co-housed with pet store mice, there is an increased number of neutrophils in the lymph nodes at steady state. These neutrophils act as reconnaissance cells to recruit additional neutrophils after infection. We observed that after infection in the foot, there is very little dissemination past the popliteal lymph node and into the peripheral organs. In four hours, the number of neutrophils in the lymph node increases dramatically from steady state. Neutrophil entry proceeds through the high endothelial venules (HEV) and can occur via direct L-selectin-Peripheral node addressin (PNAd) interactions or through a bridging mechanism involving neutrophil P-selectin glycoprotein ligand-1 (PSGL-1) and platelet- P-selectin binding to PNAd on HEV. C5a is necessary for neutrophil recruitment, but it is independent of C-C chemokine receptor type 7 (CCR7) and lymph node resident macrophages. Blocking neutrophil recruitment using anti-PNAd antibody resulted in bacterial dissemination, demonstrating the contribution of neutrophils to the innate immune function of the lymph node. Finally, this thesis begins to assess the contribution of lymph node innervation to the above processes. Sympathetic innervation may play a greater role than sensory innervation, at least as it pertains to neutrophils, as determined by the methods used here. This work still establishes an important basis for future examination of the effect of innervation on other cell types in the lymph node. Overall, this body of work has made important contributions to the understanding of neutrophil biology in the context of the lymph node, both at steady state and after infection.