Dose-dependent activation of lymphocytes in endotoxin-induced airway inflammation.
Recruitment of neutrophils to lung tissue and airspaces is a hallmark of inflammatory events following inhalation of endotoxins. We studied the role of different lymphocyte subsets in this inflammation, which is assumed to primarily involve the innate immune system. Inhalation of aerosolized Escherichia coli lipopolysaccharide (LPS) in mice induced a dose-dependent increase in neutrophils in bronchoalveolar lavage fluid, reaching a maximum after 12 h at a low dose and after 24 h at a high dose. Profiles of gene expression in lung tissue indicated an early (2 h) and transient onset of proinflammatory cytokines and chemokines by a low dose of LPS, while a high dose caused more delayed and sustained (6 to 12 h) activation. Gamma interferon, interleukin-2 (IL-2), RANTES, and the alpha chain of the IL-2 receptor were not expressed at a low dose, whereas a high dose of LPS induced a strong expression of these genes, indicating a dose-dependent activation of T cells. A similar pattern was observed for IL-17, supporting a contribution of T cells to the neutrophilic inflammation only at high-dose exposure to LPS. The involvement of lymphocytes in the inflammatory response was further studied using mice with functional deficiencies in defined lymphocyte subsets. Both gammadelta T-cell- and B-cell-deficient mice displayed a response similar to that of the corresponding wild-type strains. Selective depletion of NK cells by in vivo administration of the pk136 antibody did not significantly affect the recruitment of neutrophils into airspaces. Thus, neither NK cells, B cells, nor gammadelta T cells appeared to participate in the host response, suggesting that among the lymphocyte subsets, alphabeta T cells are exclusively involved in endotoxin-induced airway inflammation.
Larsson
R
R
Department of Biomedicine, Division of NBC Defence, Defence Research Establishment, Umeå, Sweden.
Rocksén
D
D
Lilliehöök
B
B
Jonsson
A
A
Bucht
A
A
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology
D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2