Pathways of homeostatic and emergency granulopoiesis. Top pathway: under normal conditions, G-CSF and GM-CSF regulate production of neutrophils by myeloid precursors in the bone marrow. During times of infection, the proposed emergency pathway is initiated by bacterial lipopolysaccharide (LPS) stimulation of tissue fibroblasts, stromal cells, and mononuclear phagocytes, resulting in the secretion of IL6 and M-CSF. The latter cytokine promotes cleavage of membrane IL6 receptor (mIL6R) to soluble sIL6R by ADAMs (a disintegrin and metalloproteases). The resultant soluble IL6/sIL6R complexes then circulate to the bone marrow, where they stimulate emergency granulopoiesis independent of G-CSF and GM-CSF.