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Neutrophil degranulation as crucial step in severe lung damage by Streptococcus pyogenes
Author(s) -
Soehnlein Oliver,
Herwald Heiko,
Lindbom Lennart
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a408-c
Subject(s) - lung , degranulation , chemistry , streptococcus pyogenes , immunology , inflammation , connective tissue , edema , pathology , medicine , microbiology and biotechnology , biology , staphylococcus aureus , receptor , biochemistry , genetics , bacteria
Severe infections with Streptococcus pyogenes may give rise to massive inflammatory reactions, and recent data have demonstrated a critical role of complexes formed by streptococcal M1 protein and fibrinogen in these events (Herwald et al ., Cell, 2004). Here we aimed at defining the importance of blood neutrophils (PMN) and their secretion products as well as alveolar macrophages (AM) in the lung damage caused by M1 protein. Lung tissue injury in Balbc mice at 30 min after intravenous injection of M1 protein was assessed by electron microscopy, comparison of wet weight/dry weight ratios and by analysing bronchioalveolar lavage (BAL) fluid with respect to protein content and leukocyte count. Ablation of AM was induced by intranasal application of clodronate liposomes and depletion of circulating PMN was performed by i.v. injection of RB6‐8C5 monoclonal antibody. M1 protein caused severe lung damage as characterized by PMN accumulation, tissue destruction, vascular leakage and edema formation. Depletion of either PMN or AM completely abolished lung tissue injury. Injection of neutrophil granule proteins restored the inflammatory reaction in neutropenic mice, but not in mice that were depleted of both PMN and AM. Our data demonstrate a central role of the PMN – AM axis in severe streptococcal infections. Of particular importance are neutrophil granule proteins which activate resident macrophages in the lung.