Abstract: . . .  Signaling : - target cells are macrophages and monocytes - CD 14 on cells and in the plasma binds LPS - Other cell surface receptors, such as CCR chemokine receptors and integrins may also bind LPS - Toll-like receptors (TLR) are the actual signaling receptors -> activate Nf kappaB to initiate massive cytokine synthesis (positive feedback loop) *potential therapeutic target* - TLR4 gram negative shock, TLR2 gram positive sepsis highly specific. (TLR4 KO mice do not develop shock even when injected with high levels of endotoxins) slide w/ nutmeg liver : massive amount of congestion Main culprit for low bp: NITRIC OXIDE 1. produced by endothelium and macrophages 2. NO Synthetase is induced in macrophages by numberous cytokines (iNOS) 3. deletion of cNOS (constitutive) from mice leads to systemic hypertension Mechanism : NO made by endothelial cells/macrophages diffuses through basement membrane due to gaseous properties relaxes vascular smooth muscle hypotension  . . .
. . .  actual signaling receptors -> activate Nf kappaB to initiate massive cytokine synthesis (positive feedback loop) *potential therapeutic target* - TLR4 gram negative shock, TLR2 gram positive sepsis highly specific. (TLR4 KO mice do not develop shock even when injected with high levels of endotoxins) slide w/ nutmeg liver : massive amount of congestion Main culprit for low bp: NITRIC OXIDE 1. produced by endothelium and macrophages 2. NO Synthetase is induced in macrophages by numberous cytokines (iNOS) 3. deletion of cNOS (constitutive) from mice leads to systemic hypertension Mechanism : NO made by endothelial cells/macrophages diffuses through basement membrane due to gaseous properties relaxes vascular smooth muscle hypotension  . . .
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