haemophilus somnus, a pathogen of cattle, has also been shown to display los phase variation, a characteristic which may help in the evasion of bovine host immune defenses. taken together, these observations suggest that variations in bacterial surface molecules such as los can help the pathogen evade both the humoral (antibody and complement-mediated) and the cell-mediated (killing by neutrophils, for example) host immune defenses. non-canonical pathways of lps recognition recently, it was shown that in addition to tlr4 mediated pathways, certain members of the family of the transient receptor potential ion channels recognize lps. lps-mediated activation of trpa1 was shown in mice and drosophila melanogaster flies. at higher concentrations, lps activates other members of the sensory trp channel family as well, such as trpv1, trpm3 and to some extent trpm8. lps is recognized by trpv4 on epithelial cells. trpv4 activation by lps was necessary and sufficient to induce nitric oxide production with a bactericidal effect. health effects in general the health effects of lps are due to its abilities as a potent activator and modulator of the immune system, especially its inducement of inflammation. endotoxemia the presence of endotoxins in the blood is called endotoxemia. high level of endotoxemia can lead to septic shock, while lower concentration of endotoxins in the bloodstream is called metabolic endotoxemia. endotoxemia is associated with obesity, diet, cardiovascular diseases, and diabetes, while also host genetics might have an effect. moreover, endotoxemia of intestinal origin, especially, at the host-pathogen interface, is considered to be an important factor in the development of alcoholic hepatitis, which is likely to develop on the basis of the small bowel bacterial overgrowth syndrome and an increased intestinal permeability. lipid a may cause uncontrolled activation of mammalian immune systems with production of inflammatory mediators that may lead to septic shock. this inflammatory reaction is mediated by toll-like receptor 4 which is responsible for immune system cell activation. damage to the endothelial layer of blood vessels caused by these inflammatory mediators can lead to capillary leak syndrome, dilation of blood vessels and a decrease in cardiac function and can lead to septic shock. pronounced complement activation can also be observed later in the course as the bacteria multiply in the blood. high bacterial proliferation triggering destructive endothelial damage can also lead to disseminated intravascular coagulation (dic) with loss of function of certain internal organs such as the kidneys, adrenal glands and lungs due to compromised blood supply. the skin can show the effects of vascular damage often coupled with depletion of coagulation factors in the form of petechiae, purpura and ecchymoses. the limbs can also be affected, sometimes with devastating consequences such as the development of gangrene, requiring subsequent amputation. loss of function of the adrenal glands can cause adrenal insufficiency and additional hemorrhage into the adrenals causes waterhouse-friderichsen syndrome, both of which can be life-threatening. it has also been reported that gonococcal los can cause damage to human fallopian tubes. auto-immune disease the molecular mimicry of some los molecules is thought to cause autoimmune-based host responses, such as flareups of multiple sclerosis. other examples of bacterial mimicry of host structures via los are found with the bacteria helicobacter pylori and campylobacter jejuni, organisms which cause gastrointestinal disease in humans, and haemophilus ducreyi which causes chancroid. certain c. jejuni lps serotypes (attributed to certain tetra- and pentasaccharide moieties of the core oligosaccharide) have also been implicated with guillain–barré syndrome and a variant of guillain–barré called miller-fisher syndrome. link to obesity epidemiological studies have shown that increased endotoxin load, which can be a result of increased populations of endotoxin-producing bacteria in the intestinal tract, is associated with certain obesity-related patient groups. other studies have shown that purified endotoxin from escherichia coli can induce obesity and insulin-resistance when injected into germ-free mouse models. a more recent study has uncovered a potentially contributing role for enterobacter cloacae b29 toward obesity and insulin resistance in a human patient. the presumed mechanism for the association of endotoxin with obesity is that endotoxin induces an inflammation-mediated pathway accounting for the observed obesity and insulin resistance. bacterial genera associated with endotoxin-related obesity effects include escherichia and enterobacter. depression there is experimental and observational evidence that lps might play a role in depression. administration of lps in mice can lead to depressive symptoms, and there seem to be elevated levels of lps in some people with depression. inflammation may sometimes play a role in the development of depression, and lps is pro-inflammatory. cellular senescence inflammation induced by lps can induce cellular senescence, as has been shown for the lung epithelial cells and microglial cells (the latter leading to neurodegeneration). role as contaminant in biotechnology and research lipopolysaccharides are frequent contaminants in plasmid dna prepared from bacteria or proteins expressed from bacteria, and must be removed from the dna or protein to avoid contaminating experiments and to avoid toxicity of products manufactured using industrial fermentation. ovalbumin is frequently contaminated with endotoxins. ovalbumin is one of the extensively studied proteins in animal models and also an established model allergen for airway hyper-responsiveness (ahr). commercially available ovalbumin that is contaminated with lps can falsify research results, as it does not accurately reflect the effect of the protein antigen on animal physiology. in pharmaceutical production, it is necessary to remove all traces of endotoxin from drug product containers, as even small amounts of endotoxin will cause illness in humans. a depyrogenation oven is used for this purpose. temperatures in excess of 300 °c are required to fully break down lps. the standard assay for detecting presence of endotoxin is the limulus amebocyte lysate (lal) assay, utilizing blood from the horseshoe crab (limulus polyphemus). very low levels of lps can cause coagulation of the limulus lysate due to a powerful amplification through an enzymatic cascade. however, due to the dwindling population of horseshoe crabs, and the fact that there are factors that interfere with the lal assay, efforts have been made to develop alternative assays, with the most promising ones being elisa tests using a recombinant version of a protein in the lal assay, factor c.