Imaging circulating monocytic cells fusing to endothelial cells in acutely injured and regenerating capillaries

The present studies focus on monocytic circulating cells (CCs) interacting with the endothelial cells of pulmonary capillaries in acute lung injury. The CCs are further defined into sub-sets based on their structural profiles, i.e. CC(1-3). They are shown to move into close apposition to adjacent capillary endothelium and to fuse to endothelial plasmalemmal membranes. Similarly, CCs are seen to fuse to the endothelial cells of regenerating capillaries after injury. Immunogold labeling studies demonstrate that CCs express a mediator promoting endothelial cell migration, proliferation and stability, i.e. VEGF, further supporting the potential of a paracrine interaction between the fusing cells, while the expression of CXCR4 by CCs, and of SDF-1α by adjacent endothelial cells, demonstrates a mechanism for retention of these cells at the capillary surface. Myeloid VEGF-R2(+)CD11b(+) precursors and PDGF-Rβ(+) expressing cells are identified within the CC population. The findings establish that, by fusing to endothelial cells, the monocytic CC population studied has the potential to promote capillary surface stability/integrity through a paracrine mechanism.