Acute infllammation and white blood cell production
(1986)
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- Authors
- Supervisors
- Symann, Michel
- Abstract
- Induction of acute inflammation by subcutaneous insertion of metallic copper rods in mice resulted in an increase in peripheral blood neutrophils, bone marrow granulocytes, and granulocyte-monocyte progenitor CFU-GM cells in the bone marrow, indicating that acute inflammation resulted in myeloid hyperplasia and increased bone marrow progenitors for the granulocyte-monocyte cell line. <BR> When diffusion chambers (DC) loaded with bone marrow cells were implanted into mice stimulated the day before by copper insertion, significantly more CFU-S, CFU-GM, and proliferative and non-proliferative granulocytes were produced as compared with diffusion chamber implanted into control hosts. The effect of inflammation on diffusion chamber granulopoiesis was dose related; the creation of three aseptical abscesses resulting in a higher growth rate in diffusion chamber granulopoiesis than with one abscess. This data showed that mice undergoind an inflammatory reaction elaborate stimulatory humoral factor(s) enhancing CFU-S and granulocytic growth in diffusion chamber. Moreover, there was a dose relation between the extent of inflammation and the release of these factors (s). <BR> the disappearance, using hypotonic lysis, of about 80% of the CFU-S and 40% of CFU-GM did not result in a proportional decrease in the production of diffusion chamber cells, while a greater loss in CFU-S and CFU-GM obragated the effect of the inflammation. The results suggest that in an inflammatory response, probably both CFU-S and CFU-GM are target cells of humoral factors during the stimulation phase. <BR> Transplantation experiments indicated that at least 24 hours of exposure to regulatory factors are required to observe stimulation. <BR> In mice challenged by an aseptic abscess, the serum level of colony stimulating factor(s) (CSF) capable of stimulating the in vitro growth of bone marrow progenitors CFU-GM was increased. Increased CSF occurred six hours after subcutaneous implantation of copper rods, reaching peak activity levels after 3 days and subsequently declining to normal levels. The effect of inflammation on increased serum CSF was dose related; the creation of three aseptical abscesses resulted in a higher and longer elevation of serum CSF than with one abscess. On day 3 following inflammation induction, CSF was found to increase in conjunction with the rise in bone marrow granulocyte-macrophage progenitors (173 % ± 16 of the control). These data are consistent with CSF playing a role in granulopoiesis regulation in vivo, and its being released quantitatively according to inflammation importance. <BR> From previous study, it appears that T-lymphocytes plau a central role in the regulation of hematopoiesis. To determine the role of T-lymphocytes in inflammation response, cyclosporine A (cy A), an inhibitor of T-lymphocytes function, was given in vivo, per os, 2 days before copper rod insertion. Cyclosporine A abrogated the increase in serum CSF and in bone marrow CFU-GM. These results suggest that CSF production in inflammatory probably requires the integrity of T-lymphocyte function in vivo. <BR> When diffusion chamber were implanted 4-6 days after acute inflammation induction, diffusion chamber granulopoiesis was depressed and there were significantly less DC-CFU-GM; yet the DC-CFU-S were identical to the control, whereas the levels of serum inhibitors of in vitro colony growth showed no correlation with diffusion chamber granulopoiesis inhibition. However, the bone marrow CFU-GM were reduced on day 6 after inflammation, consistent with the depressed diffusion chamber granulopoiesis. The date, as a whole, indicate that mice undergoing an inflammatory reaction first elaborate humoral stimulating factor(s) and next inhibitory factor(s) of diffusion chamber and bone marrow granulopoiesis. <BR> Furthermore, when more CFU-S were depleted than CFU-GM by hypotonic lysis, diffusion chamber cell growth inhibition was not abolished. This suggested, therefore, that CFU-GM, but not CFU-S, were the target of the inhibitors. <BR> Retransplantation studies suggested that more than 24 hours exposure to the inhibitory factor(s) is required to obtain a decrease in diffusion chamber cell growth
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