title: LFA-1, and not Mac-1, is crucial for the development of hyperreactivity in a murine model of nonallergic asthma.
abstract: In this study, we investigated the importance of the beta 2-integrins for the development of tracheal hyperreactivity in a murine model for nonallergic asthma. The response was induced by skin sensitization with dinitrofluorobenzene (DNFB) followed by an intranasal challenge with the same hapten. Twenty-four hours after the challenge, tracheal hyperreactivity, a decrease in T cells in the blood, and increased neutrophil numbers in bronchoalveolar lavage fluid (BALF) and blood were observed. Monoclonal antibodies (mAbs) directed against the alpha-chains of LFA-1 (FD441.8) and Mac-1 (M1/70) were injected intravenously 2 h before and 2 h after the challenge. Treatment with anti-LFA-1 mAb totally inhibited the development of tracheal hyperreactivity measured 24 h after the challenge, whereas anti-Mac-1 mAb had only a partial effect on this response. The decrease in T cells in the blood, which was also evident 24 h after the challenge, was totally inhibited by treatment with anti-LFA-1, whereas anti-Mac-1 had little effect. The increase in the number of neutrophils in BALF at this time point was completely inhibited by both anti-LFA-1 and anti-Mac-1. In summary, evidence presented in this report highlights the possible importance of the adhesion molecule LFA-1 in the development of tracheal hyperreactivity. Our results suggest that LFA-1 present on T cells may play an integral role in this response.
authors.affiliation: Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, The Netherlands.
authors.forename: P G
authors.initials: PG
authors.lastname: Bloemen
authors.forename: T L
authors.initials: TL
authors.lastname: Buckley
authors.forename: M C
authors.initials: MC
authors.lastname: van den Tweel
authors.forename: P A
authors.initials: PA
authors.lastname: Henricks
authors.forename: F A
authors.initials: FA
authors.lastname: Redegeld
authors.forename: A S
authors.initials: AS
authors.lastname: Koster
authors.forename: F P
authors.initials: FP
authors.lastname: Nijkamp
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001249:Asthma / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002217:Carbachol / Q000494:pharmacology; D004139:Dinitrofluorobenzene / Q000276:immunology; D007114:Immunization; D066298:In Vitro Techniques; D018655:Lymphocyte Count; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects; D012882:Skin Tests; D014132:Trachea / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology*
chemical_list: D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D002217:Carbachol; D004139:Dinitrofluorobenzene