Response to endotoxin of endotoxin-"resistant" C3H/HeJ mice: a model for study of hematopoietic control

Hematopoietic effects of bacterial Iipopolysaccharide (LPS). specifically S. typhosa LPS extracted by the Boivin (B) or Westphal (W) method, were compared in the C3H/HeJ (resistant) strain and in closely related normal strains C3H eB/FeJ and C3H/HeN. Maximal release of neutrophils from marrow to blood was normal after either LPS-B or LPS-W in C3H/HeJ. Induction of an increase in colony-stimulating factor (CSF) in serum was markedly blunted but was present after either LPS-B or LPS-W. and no evidence for this being due to an inhibitor was elicited. The effect of IPS given before sublethal irradiation on subsequent hematopoietic recovery in marrow and spleen was evaluated. LPS-W had no discernable effect on any measure of postirradiation recovery. while LPS-B influenced some but not all measures of recovery. In C3H/HeJ. LPS-B failed to have any appreciable effect on recovery of marrow neutrophils, on 4-day splenic granulocytic colonies, or on changes in numbers of transplantable spleen colony-forming cells (CFU-S). However, its effect on 1 0-day endogenous spleen colonies (E-CFU). spleen weight. and spleen iron uptake appeared to be normal. These data indicate that the C3H/HeJ mouse is a valuable model for study of control of the response of stem cells. For example, results suggest that progenitor cell response is not linked by a recognition system to changes in blood neutrophil level nor to the size of the (postmitotic) marrow pool of neutrophils. Postirradiation granulocyte recovery also appears not to be linked to the number of E-CFU. The results indicate that endotoxin has effects on multiple individual control systems and further that there is a lack of linkage between some of the control systems. T HE C3H/HeJ MOUSE is a C3H substrain that developed a genetic resistance to bacterial lipopolysacchanide (endotoxin, LPS). The present study was undertaken to explore the use of the C3H/HeJ mouse as a model for studies of control factors in hematopoiesis. The control of neutrophil production and distnibution is, at best, poorly understood, and we have even less understanding of control of the plunipotent stem cell system. LPS has been used in studies of control because it produces profound perturbation of the entire hematopoietic system. The possibility that LPS plays an in vivo role in hematopoietic regulation is under study.’ Two difficulties arise in studies of control neutrophil and plunipotent stem cell systems. First, it is difficult to separate the primary from subsequent events after endotoxin injection. Second, any putative control factor thought to be causing one of these hematologic events may contain endotoxin as a contaminant. A national sequence of events relative to the pentur