title: 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.
abstract: 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.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel;
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Petrovich
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel;
authors.forename: Sara W
authors.initials: SW
authors.lastname: Feigelson
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel;
authors.forename: Liat
authors.initials: L
authors.lastname: Stoler-Barak
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel;
authors.forename: Miki
authors.initials: M
authors.lastname: Hatzav
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel;
authors.forename: Adam
authors.initials: A
authors.lastname: Solomon
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel;
authors.forename: Amir
authors.initials: A
authors.lastname: Bar-Shai
authors.affiliation: Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel;
authors.forename: Neta
authors.initials: N
authors.lastname: Ilan
authors.affiliation: Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden; and.
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Li
authors.affiliation: Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Britta
authors.initials: B
authors.lastname: Engelhardt
authors.affiliation: Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel;
authors.forename: Israel
authors.initials: I
authors.lastname: Vlodavsky
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel; ronen.alon@weizmann.ac.il.
authors.forename: Ronen
authors.initials: R
authors.lastname: Alon
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D004731:Endotoxins / Q000633:toxicity; D005786:Gene Expression Regulation / Q000502:physiology; D005966:Glucuronidase / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced*; D039041:Integrin alpha4beta1 / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000098:blood supply; D008171:Lung Diseases / Q000139:chemically induced*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000502:physiology*; D051379:Mice; D009504:Neutrophils / Q000502:physiology*; D000099175:Heparanase
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D004731:Endotoxins; D005966:Glucuronidase; D039041:Integrin alpha4beta1; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1; D000099175:Heparanase; C480027:ICAM-2 protein, mouse
keywords: heparan sulfate; heparanase; inflammation; β2 integrin