β-Blockade protection of bone marrow following trauma: The role of G-CSF

Gregg M. Baranski, Michael D. Offin, Ziad C. Sifri, Ihab O. Elhassan, Edward J. Hannoush, Walter D. Alzate, Pranela Rameshwar, David H. Livingston, Alicia M. Mohr

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background: Following severe trauma, there is a profound elevation of catecholamine that is associated with a persistent anemic state. We have previously shown that β-blockade (βB) prevents erythroid growth suppression and decreases hematopoietic progenitor cell (HPC) mobilization following injury. Under normal conditions, granulocyte colony stimulating factor (G-CSF) triggers the activation of matrix metalloprotease-9 (MMP-9), leading to the egress of progenitor cells from the bone marrow (BM). When sustained, this depletion of BM cellularity may contribute to BM failure. This study seeks to determine if G-CSF plays a role in the βB protection of BM following trauma. Methods: Male Sprague-Dawley rats were subjected to either unilateral lung contusion (LC) ± βB, hemorrhagic shock (HS) ± βB, or both LC/HS ± βB. Propranolol (βB) was given immediately following resuscitation. Animals were sacrificed at 3 and 24 h and HPC mobilization was assessed by evaluating BM cellularity and flow cytometric analysis of peripheral blood for HPCs. The concentration of G-CSF and MMP-9 was measured in plasma by ELISA. Results: BM cellularity is decreased at 3 h following LC, HS, and LC/HS. HS and LC/HS resulted in significant HPC mobilization in the peripheral blood. The addition of βB restored BM cellularity and reduced HPC mobilization. Three h following HS and LC/HS, plasma G-CSF levels more than double, however LC alone showed no change in G-CSF. βB significantly decreased G-CSF in both HS and LC/HS. Similarly, MMP-9 is elevated following LC/HS, and βB prevents this elevation (390 ± 100 pg/mL versus 275 ± 80 pg/mL). Conclusion: βB protection of the BM following shock and injury may be due to reduced HPC mobilization and maintenance of BM cellularity. Following shock, there is an increase in plasma G-CSF and MMP-9, which is abrogated by βB and suggests a possible mechanism how βB decreases HPC mobilization thus preserving BM cellularity. In contrast, βB protection of BM following LC is not mediated by G-CSF. Therefore, the mechanism of progenitor cell mobilization from the BM is dependent on the type of injury.

Original languageEnglish (US)
Pages (from-to)325-331
Number of pages7
JournalJournal of Surgical Research
Volume170
Issue number2
DOIs
StatePublished - Oct 1 2011

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Hemorrhagic Shock
Granulocyte Colony-Stimulating Factor
Contusions
Bone Marrow
Wounds and Injuries
Hematopoietic Stem Cells
Adult Respiratory Distress Syndrome
Metalloproteases
Lung
Shock
Stem Cells
Resuscitation
Propranolol
Catecholamines
Sprague Dawley Rats
Enzyme-Linked Immunosorbent Assay
Maintenance

All Science Journal Classification (ASJC) codes

  • Surgery

Keywords

  • MMP-9
  • anemia
  • catecholamine
  • hematopoietic progenitor cells
  • propranolol

Cite this

Baranski, G. M., Offin, M. D., Sifri, Z. C., Elhassan, I. O., Hannoush, E. J., Alzate, W. D., ... Mohr, A. M. (2011). β-Blockade protection of bone marrow following trauma: The role of G-CSF. Journal of Surgical Research, 170(2), 325-331. https://doi.org/10.1016/j.jss.2011.03.059
Baranski, Gregg M. ; Offin, Michael D. ; Sifri, Ziad C. ; Elhassan, Ihab O. ; Hannoush, Edward J. ; Alzate, Walter D. ; Rameshwar, Pranela ; Livingston, David H. ; Mohr, Alicia M. / β-Blockade protection of bone marrow following trauma : The role of G-CSF. In: Journal of Surgical Research. 2011 ; Vol. 170, No. 2. pp. 325-331.
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Baranski, GM, Offin, MD, Sifri, ZC, Elhassan, IO, Hannoush, EJ, Alzate, WD, Rameshwar, P, Livingston, DH & Mohr, AM 2011, 'β-Blockade protection of bone marrow following trauma: The role of G-CSF', Journal of Surgical Research, vol. 170, no. 2, pp. 325-331. https://doi.org/10.1016/j.jss.2011.03.059

β-Blockade protection of bone marrow following trauma : The role of G-CSF. / Baranski, Gregg M.; Offin, Michael D.; Sifri, Ziad C.; Elhassan, Ihab O.; Hannoush, Edward J.; Alzate, Walter D.; Rameshwar, Pranela; Livingston, David H.; Mohr, Alicia M.

In: Journal of Surgical Research, Vol. 170, No. 2, 01.10.2011, p. 325-331.

Research output: Contribution to journalArticle

TY - JOUR

T1 - β-Blockade protection of bone marrow following trauma

T2 - The role of G-CSF

AU - Baranski, Gregg M.

AU - Offin, Michael D.

AU - Sifri, Ziad C.

AU - Elhassan, Ihab O.

AU - Hannoush, Edward J.

AU - Alzate, Walter D.

AU - Rameshwar, Pranela

AU - Livingston, David H.

AU - Mohr, Alicia M.

PY - 2011/10/1

Y1 - 2011/10/1

N2 - Background: Following severe trauma, there is a profound elevation of catecholamine that is associated with a persistent anemic state. We have previously shown that β-blockade (βB) prevents erythroid growth suppression and decreases hematopoietic progenitor cell (HPC) mobilization following injury. Under normal conditions, granulocyte colony stimulating factor (G-CSF) triggers the activation of matrix metalloprotease-9 (MMP-9), leading to the egress of progenitor cells from the bone marrow (BM). When sustained, this depletion of BM cellularity may contribute to BM failure. This study seeks to determine if G-CSF plays a role in the βB protection of BM following trauma. Methods: Male Sprague-Dawley rats were subjected to either unilateral lung contusion (LC) ± βB, hemorrhagic shock (HS) ± βB, or both LC/HS ± βB. Propranolol (βB) was given immediately following resuscitation. Animals were sacrificed at 3 and 24 h and HPC mobilization was assessed by evaluating BM cellularity and flow cytometric analysis of peripheral blood for HPCs. The concentration of G-CSF and MMP-9 was measured in plasma by ELISA. Results: BM cellularity is decreased at 3 h following LC, HS, and LC/HS. HS and LC/HS resulted in significant HPC mobilization in the peripheral blood. The addition of βB restored BM cellularity and reduced HPC mobilization. Three h following HS and LC/HS, plasma G-CSF levels more than double, however LC alone showed no change in G-CSF. βB significantly decreased G-CSF in both HS and LC/HS. Similarly, MMP-9 is elevated following LC/HS, and βB prevents this elevation (390 ± 100 pg/mL versus 275 ± 80 pg/mL). Conclusion: βB protection of the BM following shock and injury may be due to reduced HPC mobilization and maintenance of BM cellularity. Following shock, there is an increase in plasma G-CSF and MMP-9, which is abrogated by βB and suggests a possible mechanism how βB decreases HPC mobilization thus preserving BM cellularity. In contrast, βB protection of BM following LC is not mediated by G-CSF. Therefore, the mechanism of progenitor cell mobilization from the BM is dependent on the type of injury.

AB - Background: Following severe trauma, there is a profound elevation of catecholamine that is associated with a persistent anemic state. We have previously shown that β-blockade (βB) prevents erythroid growth suppression and decreases hematopoietic progenitor cell (HPC) mobilization following injury. Under normal conditions, granulocyte colony stimulating factor (G-CSF) triggers the activation of matrix metalloprotease-9 (MMP-9), leading to the egress of progenitor cells from the bone marrow (BM). When sustained, this depletion of BM cellularity may contribute to BM failure. This study seeks to determine if G-CSF plays a role in the βB protection of BM following trauma. Methods: Male Sprague-Dawley rats were subjected to either unilateral lung contusion (LC) ± βB, hemorrhagic shock (HS) ± βB, or both LC/HS ± βB. Propranolol (βB) was given immediately following resuscitation. Animals were sacrificed at 3 and 24 h and HPC mobilization was assessed by evaluating BM cellularity and flow cytometric analysis of peripheral blood for HPCs. The concentration of G-CSF and MMP-9 was measured in plasma by ELISA. Results: BM cellularity is decreased at 3 h following LC, HS, and LC/HS. HS and LC/HS resulted in significant HPC mobilization in the peripheral blood. The addition of βB restored BM cellularity and reduced HPC mobilization. Three h following HS and LC/HS, plasma G-CSF levels more than double, however LC alone showed no change in G-CSF. βB significantly decreased G-CSF in both HS and LC/HS. Similarly, MMP-9 is elevated following LC/HS, and βB prevents this elevation (390 ± 100 pg/mL versus 275 ± 80 pg/mL). Conclusion: βB protection of the BM following shock and injury may be due to reduced HPC mobilization and maintenance of BM cellularity. Following shock, there is an increase in plasma G-CSF and MMP-9, which is abrogated by βB and suggests a possible mechanism how βB decreases HPC mobilization thus preserving BM cellularity. In contrast, βB protection of BM following LC is not mediated by G-CSF. Therefore, the mechanism of progenitor cell mobilization from the BM is dependent on the type of injury.

KW - MMP-9

KW - anemia

KW - catecholamine

KW - hematopoietic progenitor cells

KW - propranolol

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Baranski GM, Offin MD, Sifri ZC, Elhassan IO, Hannoush EJ, Alzate WD et al. β-Blockade protection of bone marrow following trauma: The role of G-CSF. Journal of Surgical Research. 2011 Oct 1;170(2):325-331. https://doi.org/10.1016/j.jss.2011.03.059