TY - JOUR
T1 - Cell Behavior and Signal Molecule Involvement in a Case Study of Malignant Histiocytosis
T2 - A Negative Model of Morphine as an Immunoregulator
AU - Fricchione, Gregory L.
AU - Cytryn, Lawrence
AU - Bilfinger, Thomas V.
AU - Stefano, George B.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1997/12
Y1 - 1997/12
N2 - In a patient diagnosed with histiocytic medullary reticulosis (HM), we examined immunocytes for their responsiveness towards known signaling molecules. Both the granulocytes and monocytes were found to exhibit a high level of spontaneous activation (96% compared to normal cells 7%; P < 0.001). These cells could not be downregulated when exposed to morphine. Following patient treatment with doxorubicin and cyclophosphamide, the immunocytes still exhibited a high spontaneous activation. They responded to morphine exposure in vitro with a cell rounding and becoming immobile for only 20 min whereas normal cells would remain round and immobile for up to 1-2 h. An examination of the plasma from the HM patient revealed that monocyte colony stimulating factor (MCSF) levels were elevated (6.4 and 5.78 compared to a control range of 1-1.75 ng/ml). In the HM patient, the immunocytes did not express the opiate selective and opioid peptide insensitive receptor, μ3, supporting the lack of opiate action. Given this finding, we incubated normal monocytes with MCSF and found that it significantly reduced the μ3 Bmax. Given the role of intracellular calcium in the activation process of immunocytes, we examined the action of various calcium channel blockers for their ability to inhibit the activated HM monocytes. The agents (nimodipine, cardiazem, and verapamil; 10-9 M) were able to inhibit the HM-associated chemokinesis. Taken together, the data indicate that in the HM patient the immunocytes appear to be overactivated because stimulatory molecules are high and have the ability to downregulate the normal "braking" process. Additionally, the data indicate that MCSF deregulation may be involved as an initiating factor for this disorder.
AB - In a patient diagnosed with histiocytic medullary reticulosis (HM), we examined immunocytes for their responsiveness towards known signaling molecules. Both the granulocytes and monocytes were found to exhibit a high level of spontaneous activation (96% compared to normal cells 7%; P < 0.001). These cells could not be downregulated when exposed to morphine. Following patient treatment with doxorubicin and cyclophosphamide, the immunocytes still exhibited a high spontaneous activation. They responded to morphine exposure in vitro with a cell rounding and becoming immobile for only 20 min whereas normal cells would remain round and immobile for up to 1-2 h. An examination of the plasma from the HM patient revealed that monocyte colony stimulating factor (MCSF) levels were elevated (6.4 and 5.78 compared to a control range of 1-1.75 ng/ml). In the HM patient, the immunocytes did not express the opiate selective and opioid peptide insensitive receptor, μ3, supporting the lack of opiate action. Given this finding, we incubated normal monocytes with MCSF and found that it significantly reduced the μ3 Bmax. Given the role of intracellular calcium in the activation process of immunocytes, we examined the action of various calcium channel blockers for their ability to inhibit the activated HM monocytes. The agents (nimodipine, cardiazem, and verapamil; 10-9 M) were able to inhibit the HM-associated chemokinesis. Taken together, the data indicate that in the HM patient the immunocytes appear to be overactivated because stimulatory molecules are high and have the ability to downregulate the normal "braking" process. Additionally, the data indicate that MCSF deregulation may be involved as an initiating factor for this disorder.
KW - Granulocytes
KW - Medullary reticulosis
KW - Monocytes
KW - Morphine
KW - Mu3
UR - http://www.scopus.com/inward/record.url?scp=0031434786&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031434786&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1096-8652(199712)56:4<197::AID-AJH1>3.0.CO;2-S
DO - 10.1002/(SICI)1096-8652(199712)56:4<197::AID-AJH1>3.0.CO;2-S
M3 - Article
C2 - 9395179
AN - SCOPUS:0031434786
SN - 0361-8609
VL - 56
SP - 197
EP - 205
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 4
ER -