Lung-marginated Monocytes Modulate Pulmonary Microvascular Injury during Early Endotoxemia

Rationale: The role of monocytes in acute endotoxemia has been ascribed to systemic release of mediators within the central circulation. Little is known about the potential role of “marginated” monocytes in regulating microvascular inflammatory signaling. Objectives: To investigate whether lung-marginated monocytes can locally activate pulmonary endothelial cells through cell contact–dependent interactions in early endotoxemia. Methods: Mice were challenged with LPS to produce acute endotoxemia and pulmonary vascular injury. Adoptive transfer of ex vivo LPS-stimulated donor leukocytes to recipient mice was also performed to evaluate cell-associated inflammatory signaling between monocytes and endothelial cells within the lung. Cell suspensions from excised lungs were analyzed by flow cytometry for expression of tumor necrosis factor α (TNF-α) on monocytes and cell adhesion molecules on endothelial cells. Results: Substantial numbers of monocytes rapidly marginated to the lungs after endotoxin challenge in...