Various adhesion molecules impair microvascular leukocyte kinetics in ventilator-induced lung injury

Abstract

-Although the endothelial expression of various adhesion molecules substantially differs between pulmonary microvessels, their importance for neutrophil and lymphocyte sequestration in ventilator-induced lung injury (VILI) has not been systematically analyzed. We investigated the kinetics of polymorphonuclear cells (PMN) and mononuclear cells (MN) in the acinar microcirculation of the isolated rat lung with VILI by real-time confocal laser fluorescence microscopy, with or without inhibition of ICAM-1, VCAM-1, or P-selectin by monoclonal antibodies (MAb). Adhesion molecules in each microvessel were estimated by intravital fluorescence microscopy or immunohistochemical staining. In high tidal volume-ventilated lungs, 1) ICAM-1, VCAM-1, and P-selectin were differently upregulated in venules, arterioles, and capillaries; 2) venular PMN rolling was improved by inhibition of ICAM-1, VCAM-1, or P-selectin, whereas arteriolar PMN rolling was improved by ICAM-1 or VCAM-1 inhibition; 3) capillary PMN entrapment was ameliorated only by anti-ICAM-1 MAb; and 4) MN rolling in venules and arterioles and MN entrapment in capillaries were improved by ICAM-1 and VCAM-1 inhibition. In conclusion, the contribution of endothelial adhesion molecules to abnormal leukocyte behavior in VILI-injured microcirculation is microvessel and leukocyte specific. ICAM-1-and VCAM-1-dependent, but P-selectin-independent, arteriolar PMN rolling, which is expected to reflect the initial stage of tissue injury, should be taken as a phenomenon unique to ventilator-associated lung injury.

Activation of calpains mediates early lung neutrophilic inflammation in ventilator-induced lung injury

“…Furthermore, selective inhibition of tyrosine phosphorylation of ICAM-1 abolished mechanical stretch-induced PMN infiltration into the lung. Increased ICAM-1 protein expression has been shown to play a major role in the recruitment of PMNs in lungs during long-term mechanical ventilation (23,28). In the present study, however, we observed no alteration in ICAM-1 protein expression fol- Fig.…”

Pre-treatment with mesenchymal stem cells reduces ventilator-induced lung injury

“…Accordingly, the histopathological tissue analysis showed considerable lung injury in the animals receiving high-volume ventilation. Moreover, cell and protein analysis of BALF showed a clear pattern of VILI in the animals subjected to overstretch: 1) increased number of neutrophils, caused by augmented endothelial and epithelial permeability [1,18]; 2) reduced counts of alveolar macrophages, consistent with the rapid decline in BALF macrophages found in other works in response to high-volume ventilation [19] and attributed to their fast inflammatory activation [20]; 3) increased total protein concentration, a hallmark of leakage in the lung barrier [1,17] having an important role in neutrophil and lymphocyte sequestration in VILI [23]. Taken together, these common biomarkers of lung injury indicate that the animals subjected to high-volume ventilation and not treated with MSCs developed VILI.…”

Hypertensive stretch regulates endothelial exocytosis of Weibel-Palade bodies through VEGF receptor 2 signaling pathways

“…These observations suggest that the endothelial response to stretch stress may contribute to vascular inflammation. Consistent with this notion, excessive ventilatory strain on the lung quickly enhances the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and P-selectin [13], which are essential adhesion molecules in mediating leukocyte recruitment during inflammation. Similarly, the inflammatory endothelial responses to mechanical stretch have also been reported in intra-arterial stent implantation, in which the local vascular wall is subjected to mechanical stretch [14,15] and in grafted veins that are stretched by high arterial pressures [16].…”