Complement is required for the induction of endotoxic fever in guinea pigs and mice

Blatteis, Clark M.; Li, Shuxin; Li, Zhonghua; Perlik, Vit; Feleder, Carlos

doi:10.1016/j.jtherbio.2004.08.009

Cited by 16 publications

(15 citation statements)

References 58 publications

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“…We infer from these data that the almost immediate appearance of PGE 2 in IVC plasma after the iportal injection of LPS supports the notion, advanced previously by us (5,6,28,30), that it may be mediated by C5a rapidly induced by LPS. On the other hand, its continued production in these animals, as manifested by its further, slower rise to a higher plateau at 15 min, its delayed elevation in the C-insufficient, LPS-treated guinea pigs (Fig.…”

Section: Discussionsupporting

confidence: 89%

“…Hence, presumably, another factor rapidly evoked by LPS should drive this response. The complement (C) cascade is immediately activated in vivo by the presence of LPS (58), and we have recently reported that the anaphylatoxic complement component 5a (C5a) is an essential mediator of the febrile response to LPS (5,30). It was shown earlier that the in vitro production of PGE 2 by Kc is stimulated by C5a, whereas C depletion limits this production (15,41,48); Kc express abundant C5a receptors (14,48,61).…”

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confidence: 99%

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LPS-activated complement, not LPS per se, triggers the early release of PGE₂by Kupffer cells

Perlik¹,

Li²,

Goorha³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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The intravenous injection of LPS rapidly evokes fever. We have hypothesized that its onset is mediated by prostaglandin (PG)E2 quickly released by Kupffer cells (Kc). LPS, however, does not stimulate PGE2 production by Kc as rapidly as it induces fever; but complement (C) activated by LPS could be the exciting agent. To test this hypothesis, we injected LPS (2 or 8 g/kg) or cobra venom factor (CVF, an immediate activator of the C cascade that depletes its substrate, ultimately causing hypocomplementemia; 25 U/animal) into the portal vein of anesthetized guinea pigs and measured the appearance of PGE2, TNF-␣, IL-1␤, and IL-6 in the inferior vena cava (IVC) over the following 60 min. LPS (at both doses) and CVF induced similar rises in PGE2 within the first 5 min after treatment; the rises in PGE2 due to CVF returned to control in 15 min, whereas PGE2 rises due to LPS increased further, then stabilized. LPS given 3 h after CVF to the same animals also elevated PGE2, but after a 30-to 45-min delay. CVF per se did not alter basal PGE2 and cytokine levels and their responses to LPS. These in vivo effects were substantiated by the in vitro responses of primary Kc from guinea pigs to C (0.116 U/ml) and LPS (200 ng/ml). These results indicate that LPS-activated C rather than LPS itself triggers the early release of PGE2 by Kc. liver; fever; portal vein cannulation; cobra venom factor; pyrogenic cytokines FEVER DEVELOPS QUICKLY AFTER the intravenous bolus administration of a pyrogenic dose of LPS to conscious guinea pigs, rats, and other species, but the afferent mechanism that induces this response is controversial. It is generally thought that it is mediated by pyrogenic cytokines produced secondarily in response to the LPS challenge, rather than by its direct action. Tumor necrosis factor-␣ (TNF-␣), IL-1␤, and IL-6 are the major cytokines implicated in this response (9). There is, however, a temporal disconnect between the first appearance of these cytokines and the onset of the febrile response to intravenous LPS; that is, fever appears within 10 -15 min (13, 51) whereas TNF-␣, the first cytokine to appear, is not detectable until 30 min after LPS treatment (18,23,24,39). This temporal discrepancy is less evident after the intraperitoneal administration of low to moderate doses of LPS, when the latency of fever onset is ϳ60 min but becomes evident also when higher doses are administered, when the onset latency approaches that after intravenous LPS (7).We have shown previously that the onsets of the febrile responses to intravenous and intraperitoneal LPS are correlated with the appearance of LPS in the liver's Kupffer cells (Kc) (31), the body's principal clearinghouse of LPS (16,34,45) and source of pyrogenic cytokines (10). As cytokines are not constitutively expressed by Kc and their de novo production occurs after some delay (32), we and others have proposed, to account for the promptness of the febrile response to intravenous LPS, that the peripheral pyrogenic signal could be transmitted to the preoptic-anterior...

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Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

LPS-activated complement, not LPS per se, triggers the early release of PGE₂by Kupffer cells

Perlik¹,

Li²,

Goorha³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…One of the functions of the complement (C) system in host defense is self/non-self recognition (Blatteis et al 2004;Vukajlovich et al 1987). The lipopolysaccharides (LPSs) and outer-membrane proteins (OMPs) located on the outer membrane of Gram-negative bacteria are important targets for the bactericidal action of the complement system (Biedzka-Sarek et al 2005;Blatteis et al 2004;Hostetter 1993;Vukajlovich et al 1987).…”

Section: Introductionmentioning

confidence: 99%

“…The lipopolysaccharides (LPSs) and outer-membrane proteins (OMPs) located on the outer membrane of Gram-negative bacteria are important targets for the bactericidal action of the complement system (Biedzka-Sarek et al 2005;Blatteis et al 2004;Hostetter 1993;Vukajlovich et al 1987). The structure of the O-specific side chain of LPS and any structural change in or chemical modification of it play important roles in the resistance of bacterial cells to the lytic activity of complement (Lachowicz and Doroszkiewicz 1996;Lachowicz et al 1999;Taylor 1992).…”

Section: Introductionmentioning

confidence: 99%

“…The C3 moieties link the different complement pathways of activation and C3's fragmentation in serum give rises to C3a, C3b, iC3b, C3c, and C3d (Becherer et al 1990;Hostetter and Gordon 1987). Complement activation starts the inflammatory processes, which in some cases may end with the deteriorating effects of overreactions, as observed in endotoxin shock (Blatteis et al 2004;Hostetter 1993). Complement activation and C3 fragmentation by Proteus mirabilis S and R LPSs may enhance the inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

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Human complement activation by smooth and rough Proteus mirabilis lipopolysaccharides

Kaca

Arabski

Fudala

et al. 2009

Arch. Immunol. Ther. Exp.

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Introduction: Proteus mirabilis bacilli play an important role in human urinary tract infections, bacteremia, and rheumatoid arthritis. The authors previously studied human complement C3 conversion by smooth-form P. mirabilis O10, O23, O30, and O43 lipopolysaccharides (LPSs) and showed that smooth Proteus LPSs fragmented C3 in a dose-and time-dependent manner. In the present study, one smooth P. mirabilis S1959 and its two polysaccharide-truncated LPSs isolated from an R mutant strain were used to study the C3 conversion. Materials and Methods:The conversion of C3 to C3c by smooth and rough P. mirabilis LPSs was studied by capture ELISA and crossed immunoelectrophoresis. Proteins isolated from the outer membrane were analyzed by discontinuous sodium dodecyl sulfate gel electrophoresis. Results: The smooth P. mirabilis S1959 (O3) strain was resistant to the bactericidal activity of human serum, in contrast to the Ra and Re mutant strains. The presence of an exposed core oligosaccharide in R110 LPS was not sufficient to protect the strain from serum-dependent killing. In addition to LPS structure, the outer-membrane proteins may also play roles in protecting the smooth P. mirabilis S1959 (O3) strain from the bactericidal action of serum. It was shown that the Ra P. mirabilis R110 and the Re P. mirabilis R45 mutants possess very different OMP compositions from that of the P. mirabilis S 1959 strain. Conclusion: Regardless of the complement resistance of the P. mirabilis strains, the S1959, R110, and R45 LPSs fragmented C3 and induced C3c neo-antigen exposure. The use of complement-deficient human serum allows the conclusion that the Re-type P. mirabilis R45 LPS fragmented C3 by the antibody-independent classical pathway.

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Mechanisms of Fever Production and Lysis: Lessons from Experimental LPS Fever

Roth

Blatteis

2014

Comprehensive Physiology

151

117

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Fever is a cardinal symptom of infectious or inflammatory insults, but it can also arise from noninfectious causes. The fever-inducing agent that has been used most frequently in experimental studies designed to characterize the physiological, immunological and neuroendocrine processes and to identify the neuronal circuits that underlie the manifestation of the febrile response is lipopolysaccharide (LPS). Our knowledge of the mechanisms of fever production and lysis is largely based on this model. Fever is usually initiated in the periphery of the challenged host by the immediate activation of the innate immune system by LPS, specifically of the complement (C) cascade and Toll-like receptors. The first results in the immediate generation of the C component C5a and the subsequent rapid production of prostaglandin E2 (PGE2). The second, occurring after some delay, induces the further production of PGE2 by induction of its synthesizing enzymes and transcription and translation of proinflammatory cytokines. The Kupffer cells (Kc) of the liver seem to be essential for these initial processes. The subsequent transfer of the pyrogenic message from the periphery to the brain is achieved by neuronal and humoral mechanisms. These pathways subserve the genesis of early (neuronal signals) and late (humoral signals) phases of the characteristically biphasic febrile response to LPS. During the course of fever, counterinflammatory factors, "endogenous antipyretics," are elaborated peripherally and centrally to limit fever in strength and duration. The multiple interacting pro- and antipyretic signals and their mechanistic effects that underlie endotoxic fever are the subjects of this review.

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Complement is required for the induction of endotoxic fever in guinea pigs and mice

Cited by 16 publications

References 58 publications

LPS-activated complement, not LPS per se, triggers the early release of PGE₂by Kupffer cells

LPS-activated complement, not LPS per se, triggers the early release of PGE₂by Kupffer cells

Human complement activation by smooth and rough Proteus mirabilis lipopolysaccharides

Mechanisms of Fever Production and Lysis: Lessons from Experimental LPS Fever

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Complement is required for the induction of endotoxic fever in guinea pigs and mice

Cited by 16 publications

References 58 publications

LPS-activated complement, not LPS per se, triggers the early release of PGE2by Kupffer cells

LPS-activated complement, not LPS per se, triggers the early release of PGE2by Kupffer cells

Human complement activation by smooth and rough Proteus mirabilis lipopolysaccharides

Mechanisms of Fever Production and Lysis: Lessons from Experimental LPS Fever

Contact Info

Product

Resources

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LPS-activated complement, not LPS per se, triggers the early release of PGE₂by Kupffer cells

LPS-activated complement, not LPS per se, triggers the early release of PGE₂by Kupffer cells