title: Expression and targeting of lymphocyte function-associated antigen 1 (LFA-1) on white blood cells for treatment of allergic asthma.
abstract: Allergic asthma is a chronic respiratory disease that results from an exaggerated inflammatory response in the airways. Environment stimuli, such as pollen and HDM, cause activation and migration of inflammatory WBCs into the respiratory tract, where they cause lung damage. Migration of these WBCs is dependent on the active configuration of the β2 integrin LFA-1. The experimental therapeutic agent LtxA specifically targets active LFA-1 and causes cell death. We investigated the association between LFA-1 and allergic asthma and hypothesized that targeting LFA-1 with LtxA could be an attractive strategy for treatment of the condition. We examined LFA-1 (CD11a) levels on PBMCs from patients with allergic asthma compared with healthy controls. Patients exhibited a significantly higher percentage of PBMCs expressing LFA-1 than healthy controls. Furthermore, the level of LFA-1 expression on patient PBMCs was greater than on healthy PBMCs. We identified a unique cellular population in patients that consisted of CD4(-) CD11a(hi) cells. We also evaluated LtxA in a HDM extract-induced mouse model for allergic asthma. LtxA caused resolution of disease in mice, as demonstrated by a decrease in BALF WBCs, a reduction in pulmonary inflammation and tissue remodeling, and a decrease in proinflammatory cytokines IL-4, IL-5, IL-9, IL-17F, and IL-23α in lung tissue. LFA-1 may serve as an important marker in allergic asthma, and the elimination of activated WBCs by use of LtxA could be a viable therapeutic strategy for treating patients with this condition.
authors.affiliation: *Department of Oral Biology, Rutgers School of Dental Medicine, Newark, New Jersey, USA; Departments of Medicine, Center for Immunity and Inflammation and Division of Allergy and Immunology, and Pediatrics, Rutgers New Jersey Medical School, Newark, New Jersey, USA; and Actinobac Biomed, New Brunswick, New Jersey, USA.
authors.forename: Anukriti
authors.initials: A
authors.lastname: Gupta
authors.affiliation: *Department of Oral Biology, Rutgers School of Dental Medicine, Newark, New Jersey, USA; Departments of Medicine, Center for Immunity and Inflammation and Division of Allergy and Immunology, and Pediatrics, Rutgers New Jersey Medical School, Newark, New Jersey, USA; and Actinobac Biomed, New Brunswick, New Jersey, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Espinosa
authors.affiliation: *Department of Oral Biology, Rutgers School of Dental Medicine, Newark, New Jersey, USA; Departments of Medicine, Center for Immunity and Inflammation and Division of Allergy and Immunology, and Pediatrics, Rutgers New Jersey Medical School, Newark, New Jersey, USA; and Actinobac Biomed, New Brunswick, New Jersey, USA.
authors.forename: Lindsey E
authors.initials: LE
authors.lastname: Galusha
authors.affiliation: *Department of Oral Biology, Rutgers School of Dental Medicine, Newark, New Jersey, USA; Departments of Medicine, Center for Immunity and Inflammation and Division of Allergy and Immunology, and Pediatrics, Rutgers New Jersey Medical School, Newark, New Jersey, USA; and Actinobac Biomed, New Brunswick, New Jersey, USA.
authors.forename: Vahid
authors.initials: V
authors.lastname: Rahimian
authors.affiliation: *Department of Oral Biology, Rutgers School of Dental Medicine, Newark, New Jersey, USA; Departments of Medicine, Center for Immunity and Inflammation and Division of Allergy and Immunology, and Pediatrics, Rutgers New Jersey Medical School, Newark, New Jersey, USA; and Actinobac Biomed, New Brunswick, New Jersey, USA.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Miro
authors.affiliation: *Department of Oral Biology, Rutgers School of Dental Medicine, Newark, New Jersey, USA; Departments of Medicine, Center for Immunity and Inflammation and Division of Allergy and Immunology, and Pediatrics, Rutgers New Jersey Medical School, Newark, New Jersey, USA; and Actinobac Biomed, New Brunswick, New Jersey, USA.
authors.forename: Amariliz
authors.initials: A
authors.lastname: Rivera-Medina
authors.affiliation: *Department of Oral Biology, Rutgers School of Dental Medicine, Newark, New Jersey, USA; Departments of Medicine, Center for Immunity and Inflammation and Division of Allergy and Immunology, and Pediatrics, Rutgers New Jersey Medical School, Newark, New Jersey, USA; and Actinobac Biomed, New Brunswick, New Jersey, USA.
authors.forename: Chinnaswamy
authors.initials: C
authors.lastname: Kasinathan
authors.affiliation: *Department of Oral Biology, Rutgers School of Dental Medicine, Newark, New Jersey, USA; Departments of Medicine, Center for Immunity and Inflammation and Division of Allergy and Immunology, and Pediatrics, Rutgers New Jersey Medical School, Newark, New Jersey, USA; and Actinobac Biomed, New Brunswick, New Jersey, USA.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Capitle
authors.affiliation: *Department of Oral Biology, Rutgers School of Dental Medicine, Newark, New Jersey, USA; Departments of Medicine, Center for Immunity and Inflammation and Division of Allergy and Immunology, and Pediatrics, Rutgers New Jersey Medical School, Newark, New Jersey, USA; and Actinobac Biomed, New Brunswick, New Jersey, USA.
authors.forename: Helen A
authors.initials: HA
authors.lastname: Aguila
authors.affiliation: *Department of Oral Biology, Rutgers School of Dental Medicine, Newark, New Jersey, USA; Departments of Medicine, Center for Immunity and Inflammation and Division of Allergy and Immunology, and Pediatrics, Rutgers New Jersey Medical School, Newark, New Jersey, USA; and Actinobac Biomed, New Brunswick, New Jersey, USA kachlasc@rutgers.edu.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Kachlany
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology; D001426:Bacterial Proteins / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D040881:CD11a Antigen / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D040881:CD11a Antigen; D016207:Cytokines; D016169:Lymphocyte Function-Associated Antigen-1
keywords: CD11a; Leukothera; LtxA; house dust mite; inflammation; leukotoxin