Bone marrow-derived cells contribute to contractile dysfunction in endotoxic shock

Brian W. Binck, May F. Tsen, Miguel Islas, D. Jean White, Roger A. Schultz, Monte Willis, J. Victor Garcia, Jureta W. Horton, James A. Thomas

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

How infection precipitates depressed contractility is incompletely understood but may involve the immune, nervous, and endocrine systems as well as the heart itself. In this study, we examined the role of Toll-like receptor 4 (TLR4) in LPS-induced myocardial contractile depression. Eighteen hours following endotoxin challenge, we compared contractile responses in hearts from wild-type (WT) and TLR4-deficient mice using modified Langendorff preparations. Unlike hearts from WT mice, TLR4-deficient hearts did not reveal significant contractile dysfunction following LPS administration, as measured by decreased responses in maximal left ventricular pressure, +dP/dtmax, and -dP/dtmax in ex vivo Langendorff preparations. These findings indicate a requirement for TLR4 in LPS-induced contractile depression. To determine the contribution of bone marrow-derived TLR4 function to LPS-induced myocardial dysfunction, we generated TLR4 chimeras using adoptive transfer between histocompatible mouse strains: either TLR4-deficient mice with TLR4+/+ bone marrow-derived cells or TLR4+/+ animals lacking TLR4 in their hematopoietic cells. We then compared the contractile responses of engrafted animals after LPS challenges. Engraftment of TLR4-deficient mice with WT marrow restored sensitivity to the myocardial depressant effects of LPS in TLR4-deficient hearts (P < 0.05). Inactivation of bone marrow-derived TLR4 function, via transplantation of WT mice with TLR4-/- marrow, however, did not protect against the depressant effect of endotoxin. These findings indicate that bone marrow-derived TLR4 activity is sufficient to confer sensitivity to mice lacking TLR4 in all other tissues. However, because inactivation of marrow-derived TLR4 function alone does not protect against endotoxin-triggered contractile dysfunction, TLR4 function in other tissues may also contribute to this response.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number2 57-2
DOIs
StatePublished - Feb 1 2005
Externally publishedYes

Fingerprint

Toll-Like Receptor 4
Septic Shock
Bone Marrow Cells
Bone Marrow
Endotoxins
Endocrine System
Adoptive Transfer
Anti-Arrhythmia Agents
Ventricular Pressure
Nervous System
Mouse Tlr4 protein
Immune System
Transplantation

Keywords

  • Contractile function
  • Immune cells
  • Toll-like receptor 4

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Bone marrow-derived cells contribute to contractile dysfunction in endotoxic shock. / Binck, Brian W.; Tsen, May F.; Islas, Miguel; White, D. Jean; Schultz, Roger A.; Willis, Monte; Garcia, J. Victor; Horton, Jureta W.; Thomas, James A.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 288, No. 2 57-2, 01.02.2005.

Research output: Contribution to journalArticle

Binck, Brian W. ; Tsen, May F. ; Islas, Miguel ; White, D. Jean ; Schultz, Roger A. ; Willis, Monte ; Garcia, J. Victor ; Horton, Jureta W. ; Thomas, James A. / Bone marrow-derived cells contribute to contractile dysfunction in endotoxic shock. In: American Journal of Physiology - Heart and Circulatory Physiology. 2005 ; Vol. 288, No. 2 57-2.
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