Induction of Acute Inflammatory Lung Injury by Staphylococcal Enterotoxin B

Brigitte Neumann, Britta Engelhardt, Hermann Wagner, Bernhard Holzmann

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Superantigens stimulate T lymphocytes at high frequency by interacting with appropriate Vβ segments of the TCR. Challenge of mice with bacterial superantigens such as staphylococcal enterotoxin B (SEB) induces the systemic release cytokine resulting in septic shock and death of sensitized animals. Analysis of putative pathogenic mechanisms of T cell-dependent septic shock revealed that administration of SEB results in acute inflammatory lung injury characterized by a profound increase in vascular permeability. Injury was associated with marked leukocyte infiltration of the lung and induction of cell adhesion molecules including VCAM-1, ICAM-1, and P-selectin, but not E-selectin. Lung infiltrating leukocytes consisted of granulocytes, monuclear phagocytes and NK cells with granulocytes representing the major fraction. Consistent with a role of neutrophils as cellular mediators of inflammatory organ injury, we demonstrate activation of circulating granulocytes in mice treated with SEB. When compared with granulocytes of control mice, peripheral blood granulocytes of SEB-treated mice were found to express increased levels of cell surface Mac-1, to down-regulate expression of L-selectin and to respond with an increased production of toxic oxygen metabolites upon exposure to FMLP. Interestingly, TNF-α further enhanced FMLP-induced oxidant production by granulocytes from SEB-treated but not control mice, suggesting that the systemic response to SEB increases granulocyte sensitivity to TNF-α-mediated signals. Together, these results suggest that acute inflammatory lung injury may contribute to the pathogenesis of T cell-dependent lethal shock in mice challenged with bacterial superantigens and indicate common pathogenic mechanisms of lung injury induced by a large number of distinct inflammatory stimuli.

Original languageEnglish
Pages (from-to)1862-1871
Number of pages10
JournalJournal of Immunology
Volume158
Issue number4
StatePublished - 15 Feb 1997

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