Increased tissue factor expression on circulating monocytes in chronic HIV infection: relationship to in vivo coagulation and immune activation.
HIV infection is associated with an increased risk of thrombosis; and as antiretroviral therapy has increased the lifespan of HIV-infected patients, their risk for cardiovascular events is expected to increase. A large clinical study found recently that all-cause mortality for HIV(+) patients was related to plasma levels of interleukin-6 and to D-dimer products of fibrinolysis. We provide evidence that this elevated risk for coagulation may be related to increased proportions of monocytes expressing cell surface tissue factor (TF, thromboplastin) in persons with HIV infection. Monocyte TF expression could be induced in vitro by lipopolysaccharide and flagellin, but not by interleukin-6. Monocyte expression of TF was correlated with HIV levels in plasma, with indices of immune activation, and with plasma levels of soluble CD14, a marker of in vivo lipopolysaccharide exposure. TF levels also correlated with plasma levels of D-dimers, reflective of in vivo clot formation and fibrinolysis. Thus, drivers of immune activation in HIV disease, such as HIV replication, and potentially, microbial translocation, may activate clotting cascades and contribute to thrombus formation and cardiovascular morbidities in HIV infection.
Funderburg
Nicholas T
NT
Department of Medicine, Division of Infectious Diseases, Case Western Reserve University/University Hospitals of Cleveland, OH, USA.
Mayne
Elizabeth
E
Sieg
Scott F
SF
Asaad
Robert
R
Jiang
Wei
W
Kalinowska
Magdalena
M
Luciano
Angel A
AA
Stevens
Wendy
W
Rodriguez
Benigno
B
Brenchley
Jason M
JM
Douek
Daniel C
DC
Lederman
Michael M
MM
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis / Q000276:immunology; D005408:Flagellin / Q000494:pharmacology; D005786:Gene Expression Regulation; D006678:HIV / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000276:immunology / Q000401:mortality; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D012307:Risk Factors; D013925:Thromboplastin / Q000096:biosynthesis* / Q000276:immunology; D013927:Thrombosis / Q000097:blood* / Q000209:etiology / Q000276:immunology / Q000401:mortality; D014779:Virus Replication / Q000276:immunology
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C508600:IL6 protein, human; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C036309:fibrin fragment D; D005408:Flagellin; D013925:Thromboplastin