Induction of platelet thrombi by bacteria and antibodies.
We have characterized 2 distinct mechanisms through which infectious agents may promote platelet adhesion and thrombus formation in flowing blood, thus contributing to the progression of disease. In one case, the process initiates when the integrin alpha(IIb)beta(3) mediates platelet arrest onto immobilized bacterial constituents that have bound plasma fibrinogen. If blood contains antibodies against the bacteria, immunoglobulin (Ig) G may cluster on the same surface and activate adherent platelets through the Fc(gamma)RIIA receptor, leading to thrombus growth. As an alternative, bacteria that cannot bind fibrinogen may attach to substrates, such as immobilized plasma proteins or components of the extracellular matrix, which also support platelet adhesion. As a result of this colocalization, IgG bound to bacteria can activate neighboring platelets and induce thrombus growth regardless of their ability to initiate platelet-surface contact. Our results demonstrate that intrinsic constituents of infectious agents and host proteins play distinct but complementary roles in recruiting platelets into thrombi, possibly contributing to complications of acute and chronic infections.
Sjöbring
Ulf
U
Section for Microbiology, Immunology and Glycobiology, the Institute of Laboratory Medicine, University of Lund, Lund, Sweden. ulf.sjobring@mig.lu.se
Ringdahl
Ulrika
U
Ruggeri
Zaverio M
ZM
D000328:Adult; D000907:Antibodies, Bacterial / Q000276:immunology / Q000378:metabolism; D000942:Antigens, Bacterial; D015703:Antigens, CD / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology / Q000378:metabolism; D001792:Blood Platelets / Q000382:microbiology*; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D008954:Models, Biological; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011485:Protein Binding; D017452:Receptors, IgG / Q000378:metabolism; D013211:Staphylococcus aureus / Q000502:physiology*; D013297:Streptococcus pyogenes / Q000276:immunology / Q000502:physiology*; D013927:Thrombosis / Q000209:etiology / Q000382:microbiology*; D014774:Virulence
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; C080568:Fc gamma receptor IIA; D007074:Immunoglobulin G; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D017452:Receptors, IgG; C014689:streptococcal M protein; D005340:Fibrinogen