Preoperative granulocyte/macrophage colony-stimulating factor (GM-CSF) increases hepatic dendritic cell numbers and clustering with lymphocytes in colorectal cancer patients

Immunobiology ◽  
2006 ◽  
Vol 211 (6-8) ◽  
pp. 641-649 ◽  
Author(s):  
Steven J. Oosterling ◽  
Anneke K. Mels ◽  
Teunis B.H. Geijtenbeek ◽  
Gerben J. van der Bij ◽  
Cornelis W. Tuk ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dendritic Cell ◽  
Cancer Patients ◽  
Colony Stimulating Factor ◽  
Cell Numbers ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Colorectal Cancer Patients ◽  
Stimulating Factor

scholarly journals Propagation of dendritic cell progenitors from normal mouse liver using granulocyte/macrophage colony-stimulating factor and their maturational development in the presence of type-1 collagen.

1994 ◽  
Vol 179 (6) ◽  
pp. 1823-1834 ◽  
Author(s):  
L Lu ◽  
J Woo ◽  
A S Rao ◽  
Y Li ◽  
S C Watkins ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Mhc Class Ii ◽  
Mouse Liver ◽  
Class Ii ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Within 1 wk of liquid culture in granulocyte/macrophage colony-stimulating factor (GM-CSF), normal B10 BR (H-2k I-E+) mouse liver nonparenchymal cells (NPC) formed loosely adherent myeloid cell clusters that have been shown to contain dendritic cell (DC) progenitors in similar studies of mouse blood or bone marrow. Mononuclear cell progeny released from these clusters at and beyond 4 d exhibited distinct dendritic morphology and were actively phagocytic. After 6-10 d of culture, these cells strongly expressed CD45, CD11b, heat stable antigen, and CD44. However, the intensity of expression of the DC-restricted markers NLDC 145, 33D1, and N418, and the macrophage marker F4/80, intercellular adhesion molecule 1, and Fc gamma RII was low to moderate, whereas the cells were negative for CD3, CD45RA, and NK1.1. Splenocytes prepared in the same way also had a similar range and intensity of expression of these immunophenotypic markers. Unlike the splenic DC, however, most of the GM-CSF-propagated putative liver DC harvested at 6-10 d expressed only a low level of major histocompatibility complex (MHC) class II (I-Ek), and they failed to induce primary allogeneic responses in naive T cells, even when propagated additionally in GM-CSF and tumor necrosis alpha and/or interferon gamma-supplemented medium. However, when 7-d cultured GM-CSF-stimulated liver cells were maintained additionally for three or more days on type-1 collagen-coated plates in the continued presence of GM-CSF, they exhibited characteristics of mature DC: MHC class II expression was markedly upregulated, mixed leukocyte reaction stimulatory activity was increased, and phagocytic function was decreased. Similar observations were made when Ia+ cells were depleted from the GM-CSF-propagated cells before exposure to collagen. Further evidence that the GM-CSF-stimulated class IIdim or class II-depleted hepatic NPC were immature DC was obtained by injecting them into allogeneic B10 (H-2b I-E-) recipients. They "homed" to T cell-dependent areas of lymph nodes and spleen where they strongly expressed donor MHC class II antigen 1-5 d later. These observations provide insight into the regulation of DC maturation, and are congruent with the possibility that the migration of immature DC from normal liver and perhaps other organ allografts may help explain their inherent tolerogenicity.

Randomized, placebo-controlled, multicenter trial of granulocyte-macrophage colony-stimulating factor as infection prophylaxis in oncologic surgery. Leukine Surgical Prophylaxis Research Group.

1998 ◽  
Vol 16 (3) ◽  
pp. 1167-1173 ◽  
Author(s):  
N J Meropol ◽  
D E Wood ◽  
J Nemunaitis ◽  
N J Petrelli ◽  
B J Lipman ◽  
...  
Keyword(s):  
High Risk ◽  
Cancer Patients ◽  
Infection Prophylaxis ◽  
Colony Stimulating Factor ◽  
Postoperative Infections ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
To Receive ◽  
Stimulating Factor

PURPOSE Postoperative infections are a frequent source of preventable morbidity and mortality in the oncologic population. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent modulator of immune effector cells in vitro and in vivo. This study was conducted to determine whether GM-CSF, when administered perioperatively, could reduce the incidence of surgical infections in cancer patients. METHODS This was a prospective, randomized, placebo-controlled, multicenter study. Cancer patients at high risk of infectious surgical morbidity were randomized to receive GM-CSF 125 microg/m2 per day or placebo subcutaneously for 8 days beginning 3 days preoperatively. Routine antibiotic prophylaxis was administered to all patients. RESULTS Three hundred ninety-nine patients were enrolled, with 198 randomized to receive GM-CSF. Twenty-one percent of patients experienced infections during the first 2 weeks postoperatively, and there was no difference in infection rate between the study groups. The most common sites of infection were respiratory tract (53%) and surgical wound (25%). The duration of operation and American Society of Anesthesiology (ASA) physical status classification were the most significant predictors of infection in multivariate analysis. GM-CSF was well tolerated and was not associated with fever. CONCLUSION The eligibility criteria for this study were successful at defining a patient subgroup at high risk for postoperative infections. At an immunomodulatory dose of 125 microg/m2 per day, GM-CSF was safe and well tolerated, but did not reduce the incidence of postoperative infections in this high-risk oncologic population. Infectious morbidity in surgical oncology remains an important subject for continued clinical investigation.

scholarly journals The excess numbers of peritoneal macrophages in granulocyte-macrophage colony-stimulating factor transgenic mice are generated by local proliferation.

1992 ◽  
Vol 175 (4) ◽  
pp. 877-884 ◽  
Author(s):  
D Metcalf ◽  
M J Elliott ◽  
N A Nicola
Keyword(s):  
Transgenic Mice ◽  
Peritoneal Macrophage ◽  
Peritoneal Macrophages ◽  
Colony Stimulating Factor ◽  
Macrophage Cell ◽  
Cell Numbers ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Mice transgenic for the hemopoietic growth factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), exhibit a sustained elevation of GM-CSF levels and a 50-100-fold elevation of peritoneal macrophage cell numbers. The excess cell numbers were found to be generated in pre-adult life, with numbers remaining relatively constant thereafter. In the pre-adult period, no abnormalities were noted in the number or composition of blood, bone marrow, or spleen cells, the type or number of GM progenitor cells in the marrow or spleen, or the rate of appearance of newly formed monocytes in the peripheral blood. Peritoneal macrophages in pre-adult transgenic mice exhibited elevated mitotic activity and, after tritiated thymidine labeling, a more rapid accumulation of labeled progeny. The increase in peritoneal macrophage cell numbers appears, therefore, to be based on a GM-CSF-induced increase in local proliferative activity by peritoneal macrophages. This increased activity declined at the age of 8-10 wk, in parallel with a change in the morphology of the transgenic macrophages and an increase in binucleate and multinucleate macrophages arising by cell fusion. This change in macrophage phenotype was restricted to the transgenic mice and may therefore be a consequence of continued overstimulation by GM-CSF.

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