Complement activation alters myocellular sodium homeostasis during polymicrobial sepsis

Weiyang Wang, Ken Okamoto, Danny O. Jacobs

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective: To determine whether complement activation alters sodium homeostasis in fast-twitch skeletal muscles during sepsis, and if protein kinase-C is involved in this process. Design: Prospective, randomized, controlled animal study. Setting: Research laboratory. Subjects: Male Sprague-Dawley rats weighing 60-75 g. Interventions: Rats underwent cecal ligation and puncture (CLP) or sham-operation with or without soluble complement receptor-1 treatment. Soluble complement receptor-1 (20 mg/kg) was administered intraperitoneally 5 mins before operation. Twenty-four hours after operation, fast-twitch extensor digitorum longus muscles were isolated and incubated in normal Krebs-Henseleit buffer (pH 7.4). In addition, extensor digitorum longus muscles isolated from normal rats were incubated for 1 hr in the Krebs-Henseleit buffer media containing normal rat sera, zymosan-activated (4 or 10 mg/mL) rat sera, or heat-inactivated rat sera. Ten percent diluted rat sera were used as a complement source in all groups. Last, extensor digitorum longus muscles isolated from normal rats were incubated for 1 hr in the Krebs-Henseleit buffer media containing zymosan-activated or heat-inactivated rat sera in the presence of protein kinase-C inhibitors (i.e., 4 μM GF109203X or 5 μM rottlerin). Soluble C5b-9 complex concentrations in zymosan-activated human sera were determined by enzyme-linked immunosorbent assay to evaluate the degree of complement activation induced by zymosan. Measurements and Main Results: Incubated extensor digitorum longus muscles from CLP, sham-operated, or normal rats were used to measure intracellular Na+ and K+ contents ([Na+]i or [K+]i). Polymicrobial sepsis, as produced by CLP, markedly increased [Na+]i and [Na+]i/[K+]i ratios in fast-twitch extensor digitorum longus muscles 24 hrs after CLP compared with sham operation. Administration of soluble recombinant complement receptor 1 before operation significantly decreased myocellular [Na+]i and [Na+]i/[K+]i ratios. Zymosan profoundly elevated soluble C5b-9 concentrations in human sera in vitro. Sublytic zymosan-activated rat sera significantly increased myocellular [Na+]i and [Na+]i/[K+]i ratios relative to heat-inactivated rat sera. No difference in myocellular [Na+]i and [Na+]i/[K+]i ratios was observed when we used 4 mg/mL compared with 10 mg/mL of zymosan for activation. Last, incubation of extensor digitorum longus muscles with GF109203X or rottlerin significantly attenuated increases in myocellular [Na+]i and [Na+]i/[K+]i ratios induced by sublytic zymosan-activated rat sera. Conclusions: Polymicrobial sepsis alters sodium homeostasis in fast-twitch skeletal muscles, which is significantly attenuated by administration of soluble complement receptor 1. Protein kinase-C inhibition completely blocks changes in myocellular [Na+]i and [Na+]i/[K+]i ratios induced by sublytic zymosan-activated rat sera. Collectively, these results suggest that an inappropriate activation of complement is, at least in part, responsible for changes in skeletal muscle sodium homeostasis during sepsis, and activation of PKC is one of the intracellular signaling pathways by which complement activation alters myocellular sodium homeostasis.

Original languageEnglish (US)
Pages (from-to)684-691
Number of pages8
JournalCritical Care Medicine
Volume30
Issue number3
StatePublished - 2002
Externally publishedYes

Fingerprint

Complement Activation
Sepsis
Zymosan
Homeostasis
Sodium
Complement C1
Serum
Complement Receptors
Punctures
Muscles
Ligation
Protein Kinase C
Skeletal Muscle
Hot Temperature
Complement Membrane Attack Complex
Protein C Inhibitor
Protein Kinase Inhibitors
Sprague Dawley Rats
Enzyme-Linked Immunosorbent Assay

Keywords

  • Complement activation
  • Complement membrane attack complex
  • Critical care
  • Na-K-exchanging adenosine triphosphatase
  • Potassium
  • Protein kinase C
  • Septic shock
  • Skeletal muscle
  • Sodium
  • Zymosan

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Complement activation alters myocellular sodium homeostasis during polymicrobial sepsis. / Wang, Weiyang; Okamoto, Ken; Jacobs, Danny O.

In: Critical Care Medicine, Vol. 30, No. 3, 2002, p. 684-691.

Research output: Contribution to journalArticle

Wang, W, Okamoto, K & Jacobs, DO 2002, 'Complement activation alters myocellular sodium homeostasis during polymicrobial sepsis', Critical Care Medicine, vol. 30, no. 3, pp. 684-691.
Wang, Weiyang ; Okamoto, Ken ; Jacobs, Danny O. / Complement activation alters myocellular sodium homeostasis during polymicrobial sepsis. In: Critical Care Medicine. 2002 ; Vol. 30, No. 3. pp. 684-691.
@article{e5be8a340bfa47b9a0507019d68096fa,
title = "Complement activation alters myocellular sodium homeostasis during polymicrobial sepsis",
abstract = "Objective: To determine whether complement activation alters sodium homeostasis in fast-twitch skeletal muscles during sepsis, and if protein kinase-C is involved in this process. Design: Prospective, randomized, controlled animal study. Setting: Research laboratory. Subjects: Male Sprague-Dawley rats weighing 60-75 g. Interventions: Rats underwent cecal ligation and puncture (CLP) or sham-operation with or without soluble complement receptor-1 treatment. Soluble complement receptor-1 (20 mg/kg) was administered intraperitoneally 5 mins before operation. Twenty-four hours after operation, fast-twitch extensor digitorum longus muscles were isolated and incubated in normal Krebs-Henseleit buffer (pH 7.4). In addition, extensor digitorum longus muscles isolated from normal rats were incubated for 1 hr in the Krebs-Henseleit buffer media containing normal rat sera, zymosan-activated (4 or 10 mg/mL) rat sera, or heat-inactivated rat sera. Ten percent diluted rat sera were used as a complement source in all groups. Last, extensor digitorum longus muscles isolated from normal rats were incubated for 1 hr in the Krebs-Henseleit buffer media containing zymosan-activated or heat-inactivated rat sera in the presence of protein kinase-C inhibitors (i.e., 4 μM GF109203X or 5 μM rottlerin). Soluble C5b-9 complex concentrations in zymosan-activated human sera were determined by enzyme-linked immunosorbent assay to evaluate the degree of complement activation induced by zymosan. Measurements and Main Results: Incubated extensor digitorum longus muscles from CLP, sham-operated, or normal rats were used to measure intracellular Na+ and K+ contents ([Na+]i or [K+]i). Polymicrobial sepsis, as produced by CLP, markedly increased [Na+]i and [Na+]i/[K+]i ratios in fast-twitch extensor digitorum longus muscles 24 hrs after CLP compared with sham operation. Administration of soluble recombinant complement receptor 1 before operation significantly decreased myocellular [Na+]i and [Na+]i/[K+]i ratios. Zymosan profoundly elevated soluble C5b-9 concentrations in human sera in vitro. Sublytic zymosan-activated rat sera significantly increased myocellular [Na+]i and [Na+]i/[K+]i ratios relative to heat-inactivated rat sera. No difference in myocellular [Na+]i and [Na+]i/[K+]i ratios was observed when we used 4 mg/mL compared with 10 mg/mL of zymosan for activation. Last, incubation of extensor digitorum longus muscles with GF109203X or rottlerin significantly attenuated increases in myocellular [Na+]i and [Na+]i/[K+]i ratios induced by sublytic zymosan-activated rat sera. Conclusions: Polymicrobial sepsis alters sodium homeostasis in fast-twitch skeletal muscles, which is significantly attenuated by administration of soluble complement receptor 1. Protein kinase-C inhibition completely blocks changes in myocellular [Na+]i and [Na+]i/[K+]i ratios induced by sublytic zymosan-activated rat sera. Collectively, these results suggest that an inappropriate activation of complement is, at least in part, responsible for changes in skeletal muscle sodium homeostasis during sepsis, and activation of PKC is one of the intracellular signaling pathways by which complement activation alters myocellular sodium homeostasis.",
keywords = "Complement activation, Complement membrane attack complex, Critical care, Na-K-exchanging adenosine triphosphatase, Potassium, Protein kinase C, Septic shock, Skeletal muscle, Sodium, Zymosan",
author = "Weiyang Wang and Ken Okamoto and Jacobs, {Danny O.}",
year = "2002",
language = "English (US)",
volume = "30",
pages = "684--691",
journal = "Critical Care Medicine",
issn = "0090-3493",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Complement activation alters myocellular sodium homeostasis during polymicrobial sepsis

AU - Wang, Weiyang

AU - Okamoto, Ken

AU - Jacobs, Danny O.

PY - 2002

Y1 - 2002

N2 - Objective: To determine whether complement activation alters sodium homeostasis in fast-twitch skeletal muscles during sepsis, and if protein kinase-C is involved in this process. Design: Prospective, randomized, controlled animal study. Setting: Research laboratory. Subjects: Male Sprague-Dawley rats weighing 60-75 g. Interventions: Rats underwent cecal ligation and puncture (CLP) or sham-operation with or without soluble complement receptor-1 treatment. Soluble complement receptor-1 (20 mg/kg) was administered intraperitoneally 5 mins before operation. Twenty-four hours after operation, fast-twitch extensor digitorum longus muscles were isolated and incubated in normal Krebs-Henseleit buffer (pH 7.4). In addition, extensor digitorum longus muscles isolated from normal rats were incubated for 1 hr in the Krebs-Henseleit buffer media containing normal rat sera, zymosan-activated (4 or 10 mg/mL) rat sera, or heat-inactivated rat sera. Ten percent diluted rat sera were used as a complement source in all groups. Last, extensor digitorum longus muscles isolated from normal rats were incubated for 1 hr in the Krebs-Henseleit buffer media containing zymosan-activated or heat-inactivated rat sera in the presence of protein kinase-C inhibitors (i.e., 4 μM GF109203X or 5 μM rottlerin). Soluble C5b-9 complex concentrations in zymosan-activated human sera were determined by enzyme-linked immunosorbent assay to evaluate the degree of complement activation induced by zymosan. Measurements and Main Results: Incubated extensor digitorum longus muscles from CLP, sham-operated, or normal rats were used to measure intracellular Na+ and K+ contents ([Na+]i or [K+]i). Polymicrobial sepsis, as produced by CLP, markedly increased [Na+]i and [Na+]i/[K+]i ratios in fast-twitch extensor digitorum longus muscles 24 hrs after CLP compared with sham operation. Administration of soluble recombinant complement receptor 1 before operation significantly decreased myocellular [Na+]i and [Na+]i/[K+]i ratios. Zymosan profoundly elevated soluble C5b-9 concentrations in human sera in vitro. Sublytic zymosan-activated rat sera significantly increased myocellular [Na+]i and [Na+]i/[K+]i ratios relative to heat-inactivated rat sera. No difference in myocellular [Na+]i and [Na+]i/[K+]i ratios was observed when we used 4 mg/mL compared with 10 mg/mL of zymosan for activation. Last, incubation of extensor digitorum longus muscles with GF109203X or rottlerin significantly attenuated increases in myocellular [Na+]i and [Na+]i/[K+]i ratios induced by sublytic zymosan-activated rat sera. Conclusions: Polymicrobial sepsis alters sodium homeostasis in fast-twitch skeletal muscles, which is significantly attenuated by administration of soluble complement receptor 1. Protein kinase-C inhibition completely blocks changes in myocellular [Na+]i and [Na+]i/[K+]i ratios induced by sublytic zymosan-activated rat sera. Collectively, these results suggest that an inappropriate activation of complement is, at least in part, responsible for changes in skeletal muscle sodium homeostasis during sepsis, and activation of PKC is one of the intracellular signaling pathways by which complement activation alters myocellular sodium homeostasis.

AB - Objective: To determine whether complement activation alters sodium homeostasis in fast-twitch skeletal muscles during sepsis, and if protein kinase-C is involved in this process. Design: Prospective, randomized, controlled animal study. Setting: Research laboratory. Subjects: Male Sprague-Dawley rats weighing 60-75 g. Interventions: Rats underwent cecal ligation and puncture (CLP) or sham-operation with or without soluble complement receptor-1 treatment. Soluble complement receptor-1 (20 mg/kg) was administered intraperitoneally 5 mins before operation. Twenty-four hours after operation, fast-twitch extensor digitorum longus muscles were isolated and incubated in normal Krebs-Henseleit buffer (pH 7.4). In addition, extensor digitorum longus muscles isolated from normal rats were incubated for 1 hr in the Krebs-Henseleit buffer media containing normal rat sera, zymosan-activated (4 or 10 mg/mL) rat sera, or heat-inactivated rat sera. Ten percent diluted rat sera were used as a complement source in all groups. Last, extensor digitorum longus muscles isolated from normal rats were incubated for 1 hr in the Krebs-Henseleit buffer media containing zymosan-activated or heat-inactivated rat sera in the presence of protein kinase-C inhibitors (i.e., 4 μM GF109203X or 5 μM rottlerin). Soluble C5b-9 complex concentrations in zymosan-activated human sera were determined by enzyme-linked immunosorbent assay to evaluate the degree of complement activation induced by zymosan. Measurements and Main Results: Incubated extensor digitorum longus muscles from CLP, sham-operated, or normal rats were used to measure intracellular Na+ and K+ contents ([Na+]i or [K+]i). Polymicrobial sepsis, as produced by CLP, markedly increased [Na+]i and [Na+]i/[K+]i ratios in fast-twitch extensor digitorum longus muscles 24 hrs after CLP compared with sham operation. Administration of soluble recombinant complement receptor 1 before operation significantly decreased myocellular [Na+]i and [Na+]i/[K+]i ratios. Zymosan profoundly elevated soluble C5b-9 concentrations in human sera in vitro. Sublytic zymosan-activated rat sera significantly increased myocellular [Na+]i and [Na+]i/[K+]i ratios relative to heat-inactivated rat sera. No difference in myocellular [Na+]i and [Na+]i/[K+]i ratios was observed when we used 4 mg/mL compared with 10 mg/mL of zymosan for activation. Last, incubation of extensor digitorum longus muscles with GF109203X or rottlerin significantly attenuated increases in myocellular [Na+]i and [Na+]i/[K+]i ratios induced by sublytic zymosan-activated rat sera. Conclusions: Polymicrobial sepsis alters sodium homeostasis in fast-twitch skeletal muscles, which is significantly attenuated by administration of soluble complement receptor 1. Protein kinase-C inhibition completely blocks changes in myocellular [Na+]i and [Na+]i/[K+]i ratios induced by sublytic zymosan-activated rat sera. Collectively, these results suggest that an inappropriate activation of complement is, at least in part, responsible for changes in skeletal muscle sodium homeostasis during sepsis, and activation of PKC is one of the intracellular signaling pathways by which complement activation alters myocellular sodium homeostasis.

KW - Complement activation

KW - Complement membrane attack complex

KW - Critical care

KW - Na-K-exchanging adenosine triphosphatase

KW - Potassium

KW - Protein kinase C

KW - Septic shock

KW - Skeletal muscle

KW - Sodium

KW - Zymosan

UR - http://www.scopus.com/inward/record.url?scp=0036186072&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036186072&partnerID=8YFLogxK

M3 - Article

VL - 30

SP - 684

EP - 691

JO - Critical Care Medicine

JF - Critical Care Medicine

SN - 0090-3493

IS - 3

ER -