title: Targeting CD162 protects against streptococcal M1 protein-evoked neutrophil recruitment and lung injury.
abstract: Streptococcus pyogenes of the M1 serotype can cause streptococcal toxic shock syndrome and acute lung damage. CD162 is an adhesion molecule that has been reported to mediate neutrophil recruitment in acute inflammatory reactions. In this study, the purpose was to investigate the role of CD162 in M1 protein-provoked lung injury. Male C57BL/6 mice were treated with monoclonal antibody directed against CD162 or a control antibody before M1 protein challenge. Edema, neutrophil infiltration, and CXC chemokines were determined in the lung, 4 h after M1 protein administration. Fluorescence intravital microscopy was used to analyze leukocyte-endothelium interactions in the pulmonary microcirculation. Inhibition of CD162 reduced M1 protein-provoked accumulation of neutrophils, edema, and CXC chemokine formation in the lung by >54%. Moreover, immunoneutralization of CD162 abolished leukocyte rolling and firm adhesion in pulmonary venules of M1 protein-treated animals. In addition, inhibition of CD162 decreased M1 protein-induced capillary trapping of leukocytes in the lung microvasculature and improved microvascular perfusion in the lungs of M1 protein-treated animals. Our findings suggest that CD162 plays an important role in M1 protein-induced lung damage by regulating leukocyte rolling in pulmonary venules. Consequently, inhibition of CD162 attenuates M1 protein-evoked leukocyte adhesion and extravasation in the lung. Thus, our results suggest that targeting the CD162 might pave the way for novel opportunities to protect against pulmonary damage in streptococcal infections.
authors.affiliation: Dept. of Clinical Sciences, Malmö, Section of Surgery, Skåne Univ. Hospital, Lund Univ., 205 02 Malmö, Sweden. henrik.thorlacius@med.lu.se.
authors.forename: Songen
authors.initials: S
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Wang
authors.forename: Heiko
authors.initials: H
authors.lastname: Herwald
authors.forename: Henrik
authors.initials: H
authors.lastname: Thorlacius
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011654:Pulmonary Edema / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D019743:Chemokines, CXC; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D012333:RNA, Messenger; C014689:streptococcal M protein
keywords: adhesion; chemokines; inflammation and leukocyte