Arterial occlusion induces systemic changes in leucocyte composition

Abstract

Lack of tissue perfusion because of arterial occlusion can result in mortality and morbidity. In response to local tissue ischaemia, extravasation of leucocytes into the region at risk is initiated to facilitate matrix remodelling and subsequent perfusion recovery. However, it is unknown if local tissue ischaemia also induces a more generalized response of leucocyte trafficking and compartmentalization. This study was designed to gain insight into the temporal changes in circulating and bone marrow-derived leucocyte fractions following peripheral arterial occlusion in mice. Mouse peripheral blood and bone marrow samples were collected at baseline and subsequently at day 1, 2, 3, 4 and 7 after femoral artery ligation. Leucocyte and bone marrow cell subsets were quantified using flow cytometry. After arterial occlusion, peripheral blood leucocyte numbers did not vary significantly over time. However, significant intrinsic temporal changes in cell numbers were observed for monocytes, lymphocytes, neutrophils and their subsets with fluctuations of > 50%. Granulocytes, for example, showed an initial upregulation, while monocytes and lymphocytes numbers initially decreased. These variations in the circulation were largely preceded by changes in the corresponding bone marrow lineages. Progenitor cells of the myeloid and lymphoid lineage in the bone marrow were upregulated after the decrease in the numbers of their progeny in the peripheral blood. Local arterial occlusion results in an orchestrated systemic response of leucocyte trafficking. This response substantiates the pivotal role of leucocytes as mediators of processes leading to perfusion recovery and tissue remodelling.