Neutrophil degranulation mediates severe lung damage triggered by streptococcal M1 protein

¹ Dept. of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
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

^* To whom correspondence should be addressed. E-mail: Oliver.Sohnlein{at}ki.se.

	Abstract

Streptococcus pyogenes of the M1 serotype can cause streptococcal toxic shock syndrome commonly associated with acute lung injury. The aim of the 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 the 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 which bind to ß2-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.

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

This article has been cited by other articles:

				O. Soehnlein, L. Lindbom, and C. Weber Mechanisms underlying neutrophil-mediated monocyte recruitment Blood, November 19, 2009; 114(21): 4613 - 4623. [Abstract] [Full Text] [PDF]

				L. Johansson, A. Linner, J. Sunden-Cullberg, A. Haggar, H. Herwald, K. Lore, C.-J. Treutiger, and A. Norrby-Teglund Neutrophil-Derived Hyperresistinemia in Severe Acute Streptococcal Infections J. Immunol., September 15, 2009; 183(6): 4047 - 4054. [Abstract] [Full Text] [PDF]

				S. Oehmcke, O. Shannon, M. von Kockritz-Blickwede, M. Morgelin, A. Linder, A. I. Olin, L. Bjorck, and H. Herwald Treatment of invasive streptococcal infection with a peptide derived from human high-molecular weight kininogen Blood, July 9, 2009; 114(2): 444 - 451. [Abstract] [Full Text] [PDF]

				O. Soehnlein and L. Lindbom Neutrophil-derived azurocidin alarms the immune system J. Leukoc. Biol., March 1, 2009; 85(3): 344 - 351. [Abstract] [Full Text] [PDF]