Various adhesion molecules impair microvascular leukocyte kinetics in ventilator-induced lung injury
Naoki Miyao1, Yukio Suzuki, Kei Takeshita
1Department of Medicine, Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan.
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.
Insights
Investigating ventilator-induced lung injury (VILI), this study reveals that specific adhesion molecules like ICAM-1 and VCAM-1 uniquely impact leukocyte behavior in different lung microvessels, offering insights into VILI pathogenesis.
Area of Science:
- Pulmonary Medicine
- Cellular Biology
- Immunology
Background:
- Endothelial adhesion molecule expression varies across pulmonary microvessels.
- The role of these molecules in leukocyte sequestration during ventilator-induced lung injury (VILI) remains unclear.
Purpose of the Study:
- To systematically analyze the importance of endothelial adhesion molecules for neutrophil and lymphocyte sequestration in VILI.
- To investigate the kinetics of polymorphonuclear cells (PMN) and mononuclear cells (MN) in VILI using real-time microscopy.
Main Methods:
- Isolated rat lung model with VILI subjected to high tidal volume ventilation.
- Real-time confocal laser fluorescence microscopy to track leukocyte kinetics.
- Inhibition of ICAM-1, VCAM-1, and P-selectin using monoclonal antibodies (MAb).
- Intravital fluorescence microscopy and immunohistochemical staining to assess adhesion molecules.
Main Results:
- ICAM-1, VCAM-1, and P-selectin were differentially upregulated in venules, arterioles, and capillaries during VILI.
- PMN rolling in venules was reduced by inhibiting ICAM-1, VCAM-1, or P-selectin; arteriolar PMN rolling improved with ICAM-1 or VCAM-1 inhibition.
- Capillary PMN entrapment was reduced solely by anti-ICAM-1 MAb.
- MN rolling and capillary entrapment were improved by ICAM-1 and VCAM-1 inhibition.
Conclusions:
- Endothelial adhesion molecules contribute to leukocyte behavior in VILI-injured microcirculation in a microvessel- and leukocyte-specific manner.
- ICAM-1 and VCAM-1 mediate arteriolar PMN rolling, a potential early indicator of ventilator-associated lung injury, independent of P-selectin.
