ICAM-1 and ICAM-2 Are Differentially Expressed and Up-Regulated on Inflamed Pulmonary Epithelium, but Neither ICAM-2 nor LFA-1: ICAM-1 Are Required for Neutrophil Migration Into the Airways In Vivo

• Published in: Frontiers in immunology Vol. 12; p. 691957
• Main Authors: Chong, Deborah L W, Rebeyrol, Carine, José, Ricardo J, Williams, Andrew E, Brown, Jeremy S, Scotton, Chris J, Porter, Joanna C
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 16.08.2021
• Subjects: Animals; Antigens, CD - immunology; CD18 Antigens - immunology; Cell Adhesion Molecules - immunology; Cell Movement; Cells, Cultured; Epithelial Cells - immunology; epithelium; Humans; ICAM-1; ICAM-2; Immunology; Inflammation - immunology; Intercellular Adhesion Molecule-1 - immunology; leukocytes; lung; Lung - immunology; Lymphocyte Function-Associated Antigen-1 - immunology; Macrophages - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils - immunology; Neutrophils - physiology; Respiratory Mucosa - immunology; transmigration; Up-Regulation; lung; leukocytes; ICAM-1; epithelium; ICAM-2; transmigration
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.691957

Neutrophil migration into the airways is an important process to fight infection and is mediated by cell adhesion molecules. The intercellular adhesion molecules, ICAM-1 (CD54) and ICAM-2 (CD102) are known ligands for the neutrophil integrins, lymphocyte function associated antigen (LFA)-1 (α β ; CD11a/CD18), and macrophage-1 antigen (Mac-1;α β ;CD11b/CD18) and are implicated in leukocyte migration into the lung. However, it is ill-defined how neutrophils exit the lung and the role for ICAMs in trans-epithelial migration (TEpM) across the bronchial or alveolar epithelium. We found that human and murine alveolar epithelium expressed ICAM-1, whilst the bronchial epithelium expressed ICAM-2, and both were up-regulated during inflammatory stimulation  and in inflammatory lung diseases such as cystic fibrosis. Although β integrins interacting with ICAM-1 and -2 mediated neutrophil migration across human bronchial epithelium , neither ICAM-2 nor LFA-1 binding of ICAM-1 mediated murine neutrophil migration into the lung or broncho-alveolar space during LPS-induced inflammation Furthermore, TEpM of neutrophils themselves resulted in increased epithelial junctional permeability and reduced barrier function . This suggests that although β integrins interacting with ICAMs may regulate low levels of neutrophil traffic in healthy lung or early in inflammation when the epithelial barrier is intact; these interactions may be redundant later in inflammation when epithelial junctions are disrupted and no longer limit TEpM.