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Neutrophil degranulation mediates severe lung damage triggered by streptococcal M1 protein

¹ Dept of Physiology and Pharmacology, Karolinska Institute, Stockholm, ² Dept of Clinical Sciences, University of Lund, Lund, Sweden, ³ Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ⁴ Dept of Molecular Cell Biology, Vrije Universiteit, Amsterdam, The Netherlands.

CORRESPONDENCE: O. Soehnlein, Dept of Physiology and Pharmacology, Karolinska Institute, 17177 Stockholm, Sweden. Fax: 46 332047. E-mail: Oliver.Sohnlein{at}ki.se

Keywords: Lung injury, M1 protein, neutrophil granule proteins, Streptococcus pyogenes

Received: December 20, 2007
Accepted February 21, 2008

Streptococcus pyogenes of the M1 serotype can cause streptococcal toxic shock syndrome commonly associated with acute lung injury. The aim of the present study was to investigate the role of neutrophils and their secretion products in M1 protein-induced lung damage.

The degranulation of neutrophils by M1 protein was studied in whole blood using marker analysis for individual granule subsets. In mice, M1 protein was injected intravenously and the lung damage was assessed by histology, electron microscopy, cell count in bronchoalveolar lavage fluid and analysis of lung vascular permeability. Comparisons were made in mice with intact white blood count, neutropenic mice and neutropenic mice injected with the secretion of activated neutrophils.

In whole blood, M1 protein forms complexes with fibrinogen that bind to β₂-integrins on the neutrophil surface, resulting in degranulation of all four subsets of neutrophil granules. Intravenous injection of M1 protein into mice induced neutrophil accumulation in the lung, increase in vascular permeability and acute lung damage. Depletion of neutrophils from the circulation completely abrogated lung injury and vascular leakage. Interestingly, the lung damage was restored by injecting neutrophil secretion.

The present data suggest that neutrophil granule proteins are directly responsible for lung damage induced by the streptococcal M1 protein.

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