title: Streptococcal M1 protein-induced lung injury is independent of platelets in mice.
abstract: Streptococcus pyogenes of the M1 serotype is frequently associated with severe streptococcal infections. M1 protein challenge can cause widespread microthrombosis, suggesting a role of platelets in streptococcal sepsis. Herein, we hypothesized that platelets may play a role in M1 protein-induced lung inflammation and injury. M1 protein was injected intravenously in C57Bl/6 mice. For platelet and neutrophil depletion, an anti-GP1bα antibody and an anti-Gr-1 antibody, respectively, were administered before M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for analysis of neutrophil infiltration, edema, and macrophage inflammatory protein 2 (MIP-2) formation. Blood was collected for analysis of membrane-activated complex 1 (Mac-1) and CD40 ligand (CD40L) expression on neutrophils and platelets as well as soluble CD40L in plasma. M1 protein caused significant pulmonary damage characterized by neutrophil infiltration, increased formation of edema and MIP-2 in the lung, and enhanced Mac-1 expression on neutrophils. However, M1 protein challenge had no effect on platelet surface expression of CD40L or soluble CD40L levels in plasma. Interestingly, platelet depletion had no influence on M1 protein-induced neutrophil recruitment, MIP-2 production, and tissue damage in the lung or Mac-1 expression on neutrophils. Moreover, we observed that M1 protein could bind to neutrophils but not to platelets. On the other hand, neutrophil depletion abolished M1 protein-induced edema formation and tissue damage in the lung. Our data suggest that neutrophils but not platelets are involved in the pathophysiology of M1 protein-provoked pulmonary damage. Thus, neutrophils may constitute a key target in infections caused by S. pyogenes of the M1 serotype.
authors.affiliation: Department of Clinical Sciences, Section for Surgery, Lund University, Malmö, Sweden.
authors.forename: Su
authors.initials: S
authors.lastname: Zhang
authors.forename: Songen
authors.initials: S
authors.lastname: Zhang
authors.forename: Milladur
authors.initials: M
authors.lastname: Rahman
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 / Q000633:toxicity*; D001425:Bacterial Outer Membrane Proteins / Q000633:toxicity*; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D023201:CD40 Ligand / Q000378:metabolism; D002352:Carrier Proteins / Q000633:toxicity*; D054426:Chemokine CXCL2 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D055370:Lung Injury / Q000097:blood* / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011654:Pulmonary Edema / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D054426:Chemokine CXCL2; C014689:streptococcal M protein; D023201:CD40 Ligand