Integrin αDβ2 (CD11d/CD18) is expressed by human circulating and tissue myeloid leukocytes and mediates inflammatory signaling

• Published in: PloS one Vol. 9; no. 11; p. e112770
• Main Authors: Miyazaki, Yasunari, Vieira-de-Abreu, Adriana, Harris, Estelle S, Shah, Amrapali M, Weyrich, Andrew S, Castro-Faria-Neto, Hugo C, Zimmerman, Guy A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2014; Public Library of Science (PLoS)
• Subjects: Alveoli; Biology and Life Sciences; CD11 Antigens - metabolism; CD18 antigen; Cell adhesion & migration; Cell Differentiation; Cell spreading; Chemokines; Cytokines; Dendritic cells; Extracellular matrix; Flow Cytometry; Gene expression; Granulocytes; Humans; Inflammation; Inflammation - metabolism; Integrin alpha Chains - metabolism; Internal medicine; Leukocytes; Leukocytes (polymorphonuclear); Leukocytes - metabolism; Ligands; Lungs; Macrophages; Medicine; Medicine and Health Sciences; Monocytes; Neutrophils; Pathogens; Signal Transduction; Signaling; Brazil; Rio de Janeiro Brazil; United States > US; Utah
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0112770

Integrin α(D)β(2) is the most recently identified member of the leukocyte, or β(2), subfamily of integrin heterodimers. Its distribution and functions on human leukocytes have not been clearly defined and are controversial. We examined these issues and found that α(D)β(2) is prominently expressed by leukocytes in whole blood from healthy human subjects, including most polymorphonuclear leukocytes and monocytes. We also found that α(D)β(2) is displayed by leukocytes in the alveoli of uninjured and inflamed human lungs and by human monocyte-derived macrophages and dendritic cells, indicating broad myeloid expression. Using freshly-isolated human monocytes, we found that α(D)β(2) delivers outside-in signals to pathways that regulate cell spreading and gene expression. Screening expression analysis followed by validation of candidate transcripts demonstrated that engagement of α(D)β(2) induces mRNAs encoding inflammatory chemokines and cytokines and secretion of their protein products. Thus, α(D)β(2) is a major member of the integrin repertoire of both circulating and tissue myeloid leukocytes in humans. Its broad expression and capacity for outside-in signaling indicate that it is likely to have important functions in clinical syndromes of infection, inflammation, and tissue injury.