Lung ICAM-1 and ICAM-2 support spontaneous intravascular effector lymphocyte entrapment but are not required for neutrophil entrapment or emigration inside endotoxin-inflamed lungs

• Published in: The FASEB journal Vol. 30; no. 5; p. 1767
• Main Authors: Petrovich, Ekaterina, Feigelson, Sara W, Stoler-Barak, Liat, Hatzav, Miki, Solomon, Adam, Bar-Shai, Amir, Ilan, Neta, Li, Jin-Ping, Engelhardt, Britta, Vlodavsky, Israel, Alon, Ronen
• Format: Journal Article
• Language: English
• Published: United States 01.05.2016
• Subjects: Animals; Antigens, CD - genetics; Antigens, CD - metabolism; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Movement; Endotoxins - toxicity; Gene Expression Regulation - physiology; Glucuronidase - metabolism; Inflammation - chemically induced; Integrin alpha4beta1 - genetics; Integrin alpha4beta1 - metabolism; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Lung - blood supply; Lung Diseases - chemically induced; Lymphocyte Function-Associated Antigen-1 - genetics; Lymphocyte Function-Associated Antigen-1 - metabolism; Lymphocytes - physiology; Mice; Neutrophils - physiology; heparanase; heparan sulfate; β2 integrin; inflammation
• ISSN: 1530-6860
• DOI: 10.1096/fj.201500046

The pulmonary vasculature constitutively expresses the integrin lymphocyte function-associated antigen-1 ligands intercellular adhesion molecule (ICAM)-1 and -2. In this study, effector T cells were temporarily entrapped by the lung vasculature on their way to inflamed lymph nodes, and this entrapment was strongly reduced in ICAM-1 and -2 double-deficient mice (79 and 86% reduction for CD8(+) and CD4(+) effectors, respectively, compared with wild-type mice). Although the pulmonary vasculature has been suggested to be masked by the heparan sulfate-containing glycocalyx, which is susceptible to heparanase-mediated shedding, lung and lymphocyte heparanase have been found to be unnecessary for this entrapment. Systemic LPS induced rapid neutrophil entrapment in the lung vasculature, but in contrast to T-cell entrapment, this sequestration was ICAM-1, ICAM-2, and heparanase independent. Furthermore, neutrophil migration into the bronchoalveolar space induced by LPS inhalation and LPS-induced leakage of red blood cells into this space were not dependent on lung ICAMs or heparanase activity. Nevertheless, heparanase was critical for neutrophil accumulation in smoke-exposed lungs. Our results indicate that, whereas T cells use ICAM-1 and -2 for temporary pulmonary entrapment, neutrophils get sequestered and extravasate into inflamed lungs independent of ICAMs. This is the first demonstration that the pulmonary vasculature is differentially recognized by T cells and neutrophils.-Petrovich, E., Feigelson, S. W., Stoler-Barak, L., Hatzav, M., Solomon, A., Bar-Shai, A., Ilan, N., Li, J.-P., Engelhardt, B., Vlodavsky, I., Alon, R. Lung ICAM-1 and ICAM-2 support spontaneous intravascular effector lymphocyte entrapment but are not required for neutrophil entrapment or emigration inside endotoxin-inflamed lungs.