Further studies on the mechanism of marrow granulocytic hyperplasia in mice chronically injected with endotoxin.

Marrow granulocytic hyperplasia occurs regularly in mice injected with endotoxin for 7--30 d, despite minimal elevations of serum colony-stimulating activity (CSA). Alterations in marrow granulocyte-monocyte progenitor (CFU-C) number of changes in marrow cell cycle status do not explain this hyperplasia. We have studied other mechanisms which may explain this increased granulopoiesis. CF1, BDF1 or C57bl/6J mice were infected with 10 micrograms of S. typhosa endotoxin i.p. daily for 7--20 d. Control and endotoxin injected (tolerant) sera, each with identical levels of CSA, were assayed against control marrow cells stimulated with supramaximal amounts to CSA to assess the role of serum potentiators in augmenting granulopoiesis. In six separate experiments, tolerant sera, over a 30-fold concentration range, produced a 1.7--4.0-fold potentiation of colony growth compared to control sera (P less than 0.001). No increased tolerant sera potentiation was seen over a similar concentration range when assayed against tolerant marrow. Tolerant and control splenic conditioned media, both dialysed and non-dialysed, failed to potentiate control marrow colony growth. Tolerant marrow stem cells did not show changes in CSA sensitivity, colony size distribution or differentiation, and tolerant bone or bone marrow cells did not produce increased amounts of CSA. We conclude that serum factors separate from CSA may in part explain the increased granulopoiesis seen in endotoxin injected mice. The failure of tolerant sera to potentiate tolerant marrow growth in vitro may reflect prior in vivo exposure of marrow to these potentiating factor(s).