resulting in activation of the NETosis pathway as described above. Of note, suicidal NETosis can take hours, even with high levels of PMA stimulation, while vital NETosis that can be completed in a matter of minutes. Vital NETosis Vital NETosis can be stimulated by bacterial lipopolysaccharide (LPS), other "bacterial products, TLR4-activated platelets, or complement proteins in tandem with TLR2 ligands." Vital NETosis is made possible through the blebbing of the nucleus, resulting in a DNA-filled vesicle that is exocytosed and leaves the plasma membrane intact. Its rapid formation and release does not result in neutrophil death. It has been noted that neutrophils can continue to phagocytose and kill microbes after vital NETosis, highlighting the neutrophil's anti-microbial versatility. Regulation The formation of NETs is regulated by the lipoxygenase pathway – during certain forms of activation (including contact with bacteria) neutrophil 5-lipoxygenase forms 5-HETE-phospholipids that inhibit NET formation. Evidence from laboratory experiments suggests that NETs are cleaned away by macrophages that phagocytose and degrade them. NET-associated host damage NETs might also have a deleterious effect on the host, because the extracellular exposure of histone complexes could play a role during the development of autoimmune diseases like systemic lupus erythematosus (SLE). NETs could also play a role in inflammatory diseases, as NETs could be identified in preeclampsia, a pregnancy-related inflammatory disorder in which neutrophils are known to be activated. NETs have also been reported in the colon mucosa of patients with the inflammatory bowel disease ulcerative colitis. NETs have also been associated with the production of IgG antinuclear double stranded DNA antibodies in children infected with P. falciparum malaria. NETs have also been found in cancer patients. Preclinical research suggests that NETs are jointly responsible for cancer-related pathologies like thrombosis, organ failure and metastasis formation. NETs have been shown to contribute to the pathogenesis of HIV/SIV. NETs are capable of capturing HIV virions and destroying them. There is an increase in NET production throughout the course of HIV/SIV, which is reduced by ART. In addition, NETs are able to capture and kill various immune cell groups such as CD4+ and CD8+ T cells, B cells, and monocytes. This effect is seen not only with neutrophils in the blood, but also in various tissues such as the gut, lung, liver, and blood vessels. NETs possibly contribute to the hypercoagulable state in HIV by trapping platelets, and expressing tissue factor. NETs also have a role