title: The role of CD69 in acute neutrophil-mediated inflammation.
abstract: The leukocyte activation marker CD69 functions as a negative regulator of the immune response, both in NK-dependent tumor rejection and in the inflammation associated with lymphocyte-dependent collagen-induced arthritis. In contrast, it has been reported that CD69-deficient mice are refractory to the neutrophil-dependent acute inflammatory response associated with anti-type II collagen antibody-induced arthritis (CAIA), suggesting a positive regulatory role for CD69 in neutrophil function during arthritis induction. To clarify this discrepancy, the CAIA response was independently analyzed in our CD69-deficient mice. In these experiments, the inflammatory response was unaffected by CD69 deficiency. Additionally, the in vivo down-regulation of CD69 expression by treatment of wild-type mice with the anti-CD69 mAb 2.2, which mimics the CD69-deficient phenotype, did not affect the course of arthritis in this model. Moreover, down-regulation of CD69 expression increased expression in arthritic joints of key inflammatory mediators, including IL-1beta, IL-6 and the chemokine MCP-1. Neutrophil accumulation in zymosan-treated air pouches and in thioglycolate-treated peritoneal cavities was also unaffected in CD69-deficient mice. In addition, CD69 expression was absent in activated neutrophils. Taken together, these results rule out a significant stimulatory role for CD69 in acute inflammatory responses mediated by neutrophils.
authors.affiliation: Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Amalia
authors.initials: A
authors.lastname: Lamana
authors.forename: David
authors.initials: D
authors.lastname: Sancho
authors.forename: Aránzazu
authors.initials: A
authors.lastname: Cruz-Adalia
authors.forename: Gloria Martínez
authors.initials: GM
authors.lastname: del Hoyo
authors.forename: Ada María
authors.initials: AM
authors.lastname: Herrera
authors.forename: Manuel
authors.initials: M
authors.lastname: Feria
authors.forename: Federico
authors.initials: F
authors.lastname: Díaz-González
authors.forename: Manuel
authors.initials: M
authors.lastname: Gómez
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D001169:Arthritis, Experimental / Q000276:immunology*; D018932:Chemokine CCL2 / Q000096:biosynthesis; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D037181:Lectins, C-Type; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D015850:Interleukin-6; D037181:Lectins, C-Type; D012333:RNA, Messenger; D000099192:CD69 Antigens; C491768:Ccl2 protein, mouse