Granulocyte macrophage-colony stimulating factor and interleukin-3 are not essential for endotoxin-induced extramedullary myelopoiesis — ASN Events
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  3. Granulocyte macrophage-colony stimulating factor and interleukin-3 are not essential for endotoxin-induced extramedullary myelopoiesis

Granulocyte macrophage-colony stimulating factor and interleukin-3 are not essential for endotoxin-induced extramedullary myelopoiesis (#109)

Ming-Chin Lee 1 , Andrew D Cook 1 , Derek C Lacey 1 , John A Hamilton 1
  1. The University of Melbourne, Melbourne, VIC, Australia

Several studies have reported that splenic extramedullary haematopoiesis is important during certain inflammatory conditions. The haematopoietic growth factor, granulocyte macrophage-colony stimulating factor (GM-CSF), is known to stimulate the growth of in vitro murine macrophages from bone marrow progenitors. Current literature suggests that GM-CSF and interleukin-3 (IL-3) are implicated in regulating the survival and proliferative activity of granulocyte-monocyte progenitors (GMPs) during atherosclerosis. In the current study, we sought to determine the involvement of GM-CSF and/or IL-3 in splenic haematopoiesis following multiple intra- peritoneal (i.p) injections of endotoxin, lipopolysaccharide (LPS).

GM-CSF-/- mice and C57BL/6 wild-type (WT) mice were administered with 10 μg E.coli LPS into the peritoneal cavity for four consecutive days. In experiments using neutralizing antibodies against GM-CSF and/or IL-3, 150 μg of the neutralizing antibody was administered on day -1 and 2. Spleen, bone marrow and blood were collected and analysed using flow cytometry.

In response to endotoxin challenge, both GM-CSF-/- and WT mice displayed a comparable degree of splenomegaly, with increased total spleen cell numbers, mainly attributable to an increase in splenic myeloid lineage cells, including neutrophils and subsets of monocytes (Ly6Chi and Ly6Clo). The numbers of splenic GMPs were also significantly increased following multiple endotoxin injections in both WT and GM-CSF-/- mice. The cellular composition and number of bone marrow were unaltered following endotoxin challenge, whereas there was significant leukocytosis in peripheral blood of both WT and GM-CSF-/- mice.  Neutralizing GM-CSF and/or IL-3 in WT mice, which received multiple endotoxin injections, failed to inhibit the development of splenomegaly, in which the numbers of GMPs were again increased amongst all treatment groups.

Taken together, these results demonstrate that, while splenic extramedullary myelopoiesis may be important in supplying inflammatory cells during certain inflammatory models, it is independent of GM-CSF and IL-3 following multiple endotoxin challenges.