Lineage-c-kit+Sca-1+ Cell Response to Escherichia Coli Bacteremia in Balb/c Mice

¹ Department of Medicine, Section of Pulmonary/Critical Care Medicine, Department of Physiology, and the Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
² Department of Physiology, and the Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
³ Department of Medicine, Section of Pulmonary/Critical Care Medicine, and the Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
⁴ Department of Medicine, Section of Pulmonary/Critical Care Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA

^* To whom correspondence should be addressed. E-mail: pzhang{at}lsuhsc.edu.

Correspondence may also be addressed to David A. Welsh at dwelsh@lsuhsc.edu.

	Abstract

During bacterial infection, the bone marrow hematopoietic activity shifts toward granulocyte production, which is critical for host defenses. Along with this enhancement of granulopoiesis, the bone marrow also increases its release of hematopoietic precursors. At the present time, little is known about the commitment of hematopoietic precursor cells including hematopoietic stem cells and progenitors in this response. To investigate the hematopoietic precursor cell response to bacterial infection, bacteremia was established in Balb/c mice by intravenous injection of Escherichia coli. Bacteremia caused a 10-fold increase in the number of lineage (lin)-c-kit+Sca-1+ cells in the bone marrow. This dramatic expansion of the lin-c-kit+Sca-1+ cell pool resulted from both increased mitosis of these cells and inversion from lin-c-kit+Sca-1- cell phenotype. Lipopolysaccharide, tumor necrosis factor-, and interleukin-6 were potent factors capable of mediating phenotypic inversion of lin-c-kit+Sca-1- cells. Cells in the expanded lin-c-kit+Sca-1+ cell pool contained an increased number of colony-forming unit-granulocyte/macrophage (CFU-GM). Mobilization of lin-c-kit+Sca-1+ cells into the circulation was significantly enhanced following bacteremia. These results demonstrate that the lin-c-kit+Sca-1+ cell population in the bone marrow constitutes a key component of the host defense response to bacteremia. Functional modifications of these primitive hematopoietic precursors are critical for enhancing granulocyte production following bacterial infection.