A 59 year old man comes to the ER because of fever, shaking

[banda]

A 59 year old man comes to the ER because of fever, shaking chills for 24 hours. he completed a course of fluorouracil for a neoplasm one week ago. His temparature is 39C and BP 85/60. His HCT 30% , leukocyte count 400/mm3, platelet count 100,000 mm3. which of the following agents will most specifically complement anibiotic therapy in this patient.

a) Erythropoietin

b) GMCSF

c) IL-1

d) IL-2

e) Leucovorin.




b. GMCSF






GMCSF: (granulocyte-macrophage colony-stimulating factor) is indicated in bome marrow insufficiency caused by anti neoplasm therapy. Coipied:
GMCSF has a central role in proliferation and differentiation of hematopoetic cells. Furthermore, it influences the proliferation and migration of endothelial cells. GMCSF elicits these functions by activating a receptor consisting of a ligand-specific -chain and a -chain, which is common for GMCSF, IL-3 and IL-5. It is known that various signaling molecules such as Janus kinase 2 or transcription factors of the STAT family bind to the common -chain and initiate signaling cascades. However, -chain specific signal transduction adapters have to be postulated given that IL-3, IL-5 and GMCSF induce partly distinct biological responses. Using a yeast two-hybrid system, we identified the -chain of the GMCSF receptor as putative interaction partner of IB kinase , one of the central signaling kinases activating the transcription factor NF-B. Using endogenous protein levels of endothelial cell extracts, we could verify the interaction by co-immunoprecipitation experiments. Fluorescence resonance energy transfer (FRET) microscopy confirmed the direct interaction of CFP-IKK and YFP-GMR in living cells. Functional studies demonstrated GMCSF-dependent activation of IB kinase activity in endothelial cells, degradation of IB and activation of NF-B. Further biological studies using GMCSF-dependent TF-1 cells indicated that GMCSF-triggered activation of NF-B is important for cell survival and proliferation.



GMCSF: (granulocyte-macrophage colony-stimulating factor) is indicated in bome marrow insufficiency caused by anti neoplasm therapy.


GMCSF has a central role in proliferation and differentiation of hematopoetic cells. Furthermore, it influences the proliferation and migration of endothelial cells. GMCSF elicits these functions by activating a receptor consisting of a ligand-specific -chain and a -chain, which is common for GMCSF, IL-3 and IL-5. It is known that various signaling molecules such as Janus kinase 2 or transcription factors of the STAT family bind to the common -chain and initiate signaling cascades. However, -chain specific signal transduction adapters have to be postulated given that IL-3, IL-5 and GMCSF induce partly distinct biological responses. Using a yeast two-hybrid system, we identified the -chain of the GMCSF receptor as putative interaction partner of IB kinase , one of the central signaling kinases activating the transcription factor NF-B. Using endogenous protein levels of endothelial cell extracts, we could verify the interaction by co-immunoprecipitation experiments. Fluorescence resonance energy transfer (FRET) microscopy confirmed the direct interaction of CFP-IKK and YFP-GMR in living cells. Functional studies demonstrated GMCSF-dependent activation of IB kinase activity in endothelial cells, degradation of IB and activation of NF-B. Further biological studies using GMCSF-dependent TF-1 cells indicated that GMCSF-triggered activation of NF-B is important for cell survival and proliferation.