Streptococcal M1 Protein-Provoked CXC Chemokine Formation, Neutrophil Recruitment and Lung Damage Are Regulated by Rho-Kinase Signaling

• Published in: Journal of innate immunity Vol. 4; no. 4; pp. 399 - 408
• Main Authors: Zhang, Songen, Rahman, Milladur, Zhang, Su, Herwald, Heiko, Qi, Zhongquan, Jeppsson, Bengt, Thorlacius, Henrik
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01-01-2012; S. Karger AG
• Subjects: Animals; Antigens, Bacterial - immunology; Bacterial diseases; Bacterial Outer Membrane Proteins - immunology; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Basic Medicine; Biological and medical sciences; Carrier Proteins - immunology; Chemokines, CXC - biosynthesis; Chemokines, CXC - genetics; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Regulation; General aspects; Genetics of the immune response; Human bacterial diseases; Humans; Immunobiology; Immunologi inom det medicinska området; Immunology in the medical area; Infectious diseases; Lung - immunology; Lung - metabolism; Lung - pathology; Macrophages, Alveolar - immunology; Male; Mathematics in biology. Statistical analysis. Models. Metrology. Data processing in biology (general aspects); Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Mice; Mice, Inbred C57BL; Neutrophil Infiltration - immunology; Neutrophils - immunology; Pulmonary Edema - immunology; Pulmonary Edema - pathology; Research Article; rho-Associated Kinases - metabolism; Signal Transduction; Staphylococcal infections, streptococcal infections, pneumococcal infections; Streptococcus pyogenes; Sepsis; Leukocytes; Kinases; Lung; Chemokines; Enzyme; Leukocyte; Transferases; Cytokine; Granulocyte; Natural immunity; Respiratory system; Protein; Recruitment; Infection; Sepsis syndrome; Signal transduction; Kinase; Streptococcal infection; Bacteriosis; Lesion; Neutrophil; CXC chemokine
• ISSN: 1662-811X; 1662-8128
• DOI: 10.1159/000336182

Streptococcal toxic shock syndrome is frequently caused by Streptococcus pyogenes of the M1 serotype. The aim of this study was to determine the role of Ras-homologous (Rho)-kinase signaling in M1 protein-provoked lung damage. Male C57BL/6 mice received the Rho-kinase-specific inhibitor Y-27632 before administration of M1 protein. Edema, neutrophil accumulation and CXC chemokines were quantified in the lung 4 h after M1 protein challenge. Flow cytometry was used to determine Mac-1 expression. Quantitative RT-PCR was used to determine gene expression of CXC chemokine mRNA in alveolar macrophages. M1 protein increased neutrophil accumulation, edema and CXC chemokine formation in the lung as well as enhanced Mac-1 expression on neutrophils. Inhibition of Rho-kinase signaling significantly reduced M1 protein-provoked neutrophil accumulation and edema formation in the lung. M1 protein-triggered pulmonary production of CXC chemokine and gene expression of CXC chemokines in alveolar macrophages was decreased by Y-27632. Moreover, Rho-kinase inhibition attenuated M1 protein-induced Mac-1 expression on neutrophils. We conclude that Rho-kinase-dependent neutrophil infiltration controls pulmonary tissue damage in response to streptococcal M1 protein and that Rho-kinase signaling regulates M1 protein-induced lung recruitment of neutrophils via the formation of CXC chemokines and Mac-1 expression.