title: Integrin αDβ2 (CD11d/CD18) is expressed by human circulating and tissue myeloid leukocytes and mediates inflammatory signaling.
abstract: 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.
authors.affiliation: Department of Respiratory Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84112, United States of America; Laboratório de Immunofarmacologia, Instituto Oswaldo Cruz, Fundacão Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Vieira-de-Abreu
authors.affiliation: Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84112, United States of America.
authors.forename: Estelle S
authors.initials: ES
authors.lastname: Harris
authors.affiliation: Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84112, United States of America.
authors.forename: Amrapali M
authors.initials: AM
authors.lastname: Shah
authors.affiliation: Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84112, United States of America; Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84112, United States of America.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Weyrich
authors.affiliation: Laboratório de Immunofarmacologia, Instituto Oswaldo Cruz, Fundacão Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Hugo C
authors.initials: HC
authors.lastname: Castro-Faria-Neto
authors.affiliation: Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84112, United States of America; Laboratório de Immunofarmacologia, Instituto Oswaldo Cruz, Fundacão Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Zimmerman
mesh_terms: D018845:CD11 Antigens / Q000378:metabolism*; D002454:Cell Differentiation; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D039001:Integrin alpha Chains / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018845:CD11 Antigens; C406812:ITGAD protein, human; D039001:Integrin alpha Chains