title: Role of beta 1, beta 2 integrins and ICAM-1 in lung injury after deposition of IgG and IgA immune complexes.
abstract: After intrapulmonary deposition of IgG or IgA immune complexes, injury has been recently shown to be CD18-dependent in both cases and E-selection-dependent only in the former case. In our studies further evaluation of the requirements for beta 1 and beta 2 integrins and intercellular adhesion molecule-1 (ICAM-1) has been undertaken. In the IgG immune complex model, which is neutrophil dependent, anti-CD11a reduced injury (as measured by changes in permeability and hemorrhage) by 61 and 43%, respectively, whereas a newly developed anti-CD11b produced minimal protection (16 and 19%, respectively). Treatment of rats with increasing doses (1.5- and 3.0-fold) of antibody to rat CD11b failed to demonstrate additional protective effects in this model of injury. Anti-ICAM-1 reduced the parameters of injury by 61 and 78%, respectively, while anti-VLA-4 reduced the injury parameters by 40 and 35%, respectively. There were reductions in lung content of myeloperoxidase, roughly corresponding to the protective effects of the interventions. In the IgA immune complex model of injury, in which lung macrophages appear to be the effector cells, anti-CD11a reduced the injury parameters (permeability and hemorrhage) by 36 and 33%, respectively, whereas anti-CD11b reduced the parameters of injury by 63 and 67%, respectively. In this model, anti-ICAM-1 reduced the parameters of injury by 61 and 56%, respectively, while anti-VLA-4 reduced the parameters by 77 and 62%, respectively. The cell content of bronchoalveolar lavage fluids revealed changes that have been shown to reflect protective interventions in both models of immune complex-induced injury. These findings suggest that, in IgG and IgA immune complex models of lung injury, both VLA-4 and ICAM-1 are required, although lymphocyte function-associated Ag-1 is the predominant beta 2 integrin requirement in the IgG immune complex-induced model of injury and Mac-1 is the predominant requirement for IgA immune complex-induced lung injury. Thus, engagement in the lung of adhesion molecules in a manner leading to injury depends on the nature of the inflammatory stimulus and the type of phagocytic cells involved in the development of injury.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
authors.forename: M S
authors.initials: MS
authors.lastname: Mulligan
authors.forename: G P
authors.initials: GP
authors.lastname: Wilson
authors.forename: R F
authors.initials: RF
authors.lastname: Todd
authors.forename: C W
authors.initials: CW
authors.lastname: Smith
authors.forename: D C
authors.initials: DC
authors.lastname: Anderson
authors.forename: J
authors.initials: J
authors.lastname: Varani
authors.forename: T B
authors.initials: TB
authors.lastname: Issekutz
authors.forename: M
authors.initials: M
authors.lastname: Miyasaka
authors.forename: T
authors.initials: T
authors.lastname: Tamatani
authors.forename: M
authors.initials: M
authors.lastname: Myasaka
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000627:therapeutic use; D000936:Antigen-Antibody Complex / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000473:pathology; D018845:CD11 Antigens; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D007070:Immunoglobulin A / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D019012:Integrin beta1; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000473:pathology*; D011817:Rabbits; D051381:Rats
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D018845:CD11 Antigens; D015815:Cell Adhesion Molecules; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D019012:Integrin beta1; D016023:Integrins; D018799:Intercellular Adhesion Molecule-1