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Title: Cutaneous mast cell maturation does not depend on an intact bone marrow microenvironment

Abstract

A study was made to determine whether the maturation of murine cutaneous mast cells from stem cells depends on an intact bone marrow microenvironment. Normal bone marrow cells (+/+) were infused into 2 groups of mast cell-deficient mice: WBB6F1-W/Wv mice and /sup 89/Sr-pretreated W/Wv mice. /sup 89/Sr is a long-lived bone-seeking radioisotope which provides continuous irradiation of the marrow and thereby ablates the marrow microenvironment. Skin biopsies revealed that the /sup 89/Sr-pretreated mice and the controls had repopulated their skin with mast cells equally well. Natural killer cell function was significantly depressed in the /sup 89/Sr-treated mice, confirming that the marrow microenvironment had been functionally altered. It appears that, although the precursors for cutaneous mast cells are marrow derived, they do not need an intact marrow microenvironment for maturation.

Authors:
; ; ; ;
Publication Date:
Research Org.:
Univ. of Texas Health Science Center, Dallas
OSTI Identifier:
6628610
Alternate Identifier(s):
OSTI ID: 6628610
Resource Type:
Journal Article
Resource Relation:
Journal Name: J. Invest. Dermatol.; (United States); Journal Volume: 82:1
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; BONE MARROW; INTERNAL IRRADIATION; MAST CELLS; CELL DIFFERENTIATION; ANIMAL CELLS; BIOLOGICAL RADIATION EFFECTS; CYTOLOGY; MICE; SKIN; STEM CELLS; STRONTIUM 89; ALKALINE EARTH ISOTOPES; ANIMAL TISSUES; ANIMALS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BIOLOGICAL EFFECTS; BIOLOGY; BODY; CONNECTIVE TISSUE CELLS; DAYS LIVING RADIOISOTOPES; EVEN-ODD NUCLEI; HEMATOPOIETIC SYSTEM; INTERMEDIATE MASS NUCLEI; IRRADIATION; ISOTOPES; MAMMALS; NUCLEI; ORGANS; RADIATION EFFECTS; RADIOISOTOPES; RODENTS; SOMATIC CELLS; STRONTIUM ISOTOPES; TISSUES; VERTEBRATES 560162* -- Radionuclide Effects, Kinetics, & Toxicology-- Animals, Plants, Microorganisms, & Cells

Citation Formats

Charley, M.R., Mikhael, A., Sontheimer, R.D., Gilliam, J.N., and Bennett, M. Cutaneous mast cell maturation does not depend on an intact bone marrow microenvironment. United States: N. p., 1984. Web. doi:10.1111/1523-1747.ep12259043.
Charley, M.R., Mikhael, A., Sontheimer, R.D., Gilliam, J.N., & Bennett, M. Cutaneous mast cell maturation does not depend on an intact bone marrow microenvironment. United States. doi:10.1111/1523-1747.ep12259043.
Charley, M.R., Mikhael, A., Sontheimer, R.D., Gilliam, J.N., and Bennett, M. Sun . "Cutaneous mast cell maturation does not depend on an intact bone marrow microenvironment". United States. doi:10.1111/1523-1747.ep12259043.
@article{osti_6628610,
title = {Cutaneous mast cell maturation does not depend on an intact bone marrow microenvironment},
author = {Charley, M.R. and Mikhael, A. and Sontheimer, R.D. and Gilliam, J.N. and Bennett, M.},
abstractNote = {A study was made to determine whether the maturation of murine cutaneous mast cells from stem cells depends on an intact bone marrow microenvironment. Normal bone marrow cells (+/+) were infused into 2 groups of mast cell-deficient mice: WBB6F1-W/Wv mice and /sup 89/Sr-pretreated W/Wv mice. /sup 89/Sr is a long-lived bone-seeking radioisotope which provides continuous irradiation of the marrow and thereby ablates the marrow microenvironment. Skin biopsies revealed that the /sup 89/Sr-pretreated mice and the controls had repopulated their skin with mast cells equally well. Natural killer cell function was significantly depressed in the /sup 89/Sr-treated mice, confirming that the marrow microenvironment had been functionally altered. It appears that, although the precursors for cutaneous mast cells are marrow derived, they do not need an intact marrow microenvironment for maturation.},
doi = {10.1111/1523-1747.ep12259043},
journal = {J. Invest. Dermatol.; (United States)},
number = ,
volume = 82:1,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 1984},
month = {Sun Jan 01 00:00:00 EST 1984}
}
  • Two different types of cells in the peritoneal cavity of mice produce mast cell colonies in methylcellulose. Large mast cell colonies are produced by bone marrow-derived precursors resembling lymphoid cells by light microscopy (L-CFU-Mast), whereas medium and small mast cell colonies are produced by morphologically identifiable mast cells (M-CFU-Mast and S-CFU-Mast, respectively). In the present study we eradicated peritoneal mast cells by intraperitoneal (IP) injection of distilled water. The regeneration process was investigated to clarify the relationship between L-CFU-Mast, M-CFU-Mast, and S-CFU-Mast. After injection of distilled water, M-CFU-Mast and S-CFU-Mast disappeared, but L-CFU-Mast increased, and then M-CFU-Mast and S-CFU-Mast appeared,more » suggesting the presence of a hierarchic relationship. When purified peritoneal mast cells were injected two days after the water injection, the L-CFU-Mast did not increase. In the peritoneal cavity of WBB6F1-+/+ mice that had been lethally irradiated and rescued by bone marrow cells of C57BL/6-bgJ/bgJ (beige, Chediak-Higashi syndrome) mice, L-CFU-Mast were of bgJ/bgJ type, but M-CFU-Mast and S-CFU-Mast were of +/+ type. The injection of distilled water to the radiation chimeras resulted in the development of bgJ/bgJ-type M-CFU-Mast and then S-CFU-Mast. The presence of mast cells appeared to suppress the recruitment of L-CFU-Mast from the bloodstream and to inhibit the differentiation of L-CFU-Mast to M-CFU-Mast.« less
  • The multiple myeloma (MM) bone marrow (BM) microenvironment plays a critical role in supporting tumor growth and survival as well as in promoting formation of osteolytic lesions. Recent results suggest that the p38 mitogen-activated protein kinase (MAPK) is an important factor in maintaining this activated environment. In this report, we demonstrate that the p38{alpha} MAPK inhibitor, SCIO-469, suppresses secretion of the tumor-supportive factors IL-6 and VEGF from BM stromal cells (BMSCs) as well as cocultures of BMSCs with MM cells, resulting in reduction in MM cell proliferation. Additionally, we show that SCIO-469 prevents TNF{alpha}-induced adhesion of MM cells to BMSCsmore » through an ICAM-1- and VCAM-1-independent mechanism. Microarray analysis revealed a novel set of TNF{alpha}-induced chemokines in BMSCs that is strongly inhibited by SCIO-469. Furthermore, reintroduction of chemokines CXCL10 and CCL8 to BMSCs overcomes the inhibitory effect of SCIO-469 on TNF{alpha}-induced MM adhesion. Lastly, we show that SCIO-469 inhibits secretion and expression of the osteoclast-activating factors IL-11, RANKL, and MIP-1{alpha} as well as prevents human osteoclast formation in vitro. Collectively, these results suggest that SCIO-469 treatment can suppress factors in the bone marrow microenvironment to inhibit MM cell proliferation and adhesion and also to alleviate osteolytic activation in MM.« less
  • Purpose: To characterize the tumor microenvironment after standard radiation therapy (SRT) and pulsed radiation therapy (PRT) in Lewis lung carcinoma (LLC) allografts. Methods and Materials: Subcutaneous LLC tumors were established in C57BL/6 mice. Standard RT or PRT was given at 2 Gy/d for a total dose of 20 Gy using a 5 days on, 2 days off schedule to mimic clinical delivery. Radiation-induced tumor microenvironment changes were examined after treatment using flow cytometry and antibody-specific histopathology. Normal tissue effects were measured using noninvasive {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography after naïve animals were given whole-lung irradiation to 40 Gy in 4 weeks using the same 2-Gy/dmore » regimens. Results: Over the 2 weeks of therapy, PRT was more effective than SRT at reducing tumor growth rate (0.31 ± 0.02 mm{sup 3}/d and 0.55 ± 0.04 mm{sup 3}/d, respectively; P<.007). Histopathology showed a significant comparative reduction in the levels of Ki-67 (14.5% ± 3%), hypoxia (10% ± 3.5%), vascular endothelial growth factor (2.3% ± 1%), and stromal-derived factor-1α (2.5% ± 1.4%), as well as a concomitant decrease in CD45{sup +} bone marrow–derived cell (BMDC) migration (7.8% ± 2.2%) after PRT. The addition of AMD3100 also decreased CD45{sup +} BMDC migration in treated tumors (0.6% ± 0.1%). Higher vessel density was observed in treated tumors. No differences were observed in normal lung tissue after PRT or SRT. Conclusions: Pulsed RT–treated tumors exhibited slower growth and reduced hypoxia. Pulsed RT eliminated initiation of supportive mechanisms utilized by tumors in low oxygen microenvironments, including angiogenesis and recruitment of BMDCs.« less
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  • Although tissue mast cells are derived from the bone marrow, some descendants of bone marrow-derived precursors retain the ability to proliferate and differentiate into mast cells even after localization in the skin. The purpose of the present study was to determine the D0 values for mast-cell precursors in the bone marrow and those localized in the skin. Bone marrow cells were removed from (WB X C57BL/6)F1-+/+ mice after various doses of irradiation and injected into the skin of the congenic W/Wv mice which were genetically without mast cells. Radiosensitivity of mast-cell precursors in the bone marrow was evaluated by determiningmore » the proportion of the injection sites at which mast cells did not appear. For the assay of the radiosensitivity of mast-cell precursors localized in the skin, pieces of skin were removed from beige C57BL/6 (bgJ/bgJ. Chediak-Higashi syndrome) mice after various doses of irradiation and grafted onto the back of the normal C57BL/6 mice. Radiosensitivity of mast-cell precursors in the skin was evaluated by determining the decrease of beige-type mast cells which possessed giant granules. Mast-cell precursors in the bone marrow were much more radiosensitive than those localized in the skin. D0 value was about 100 rad for the former and about 800 rad for the latter.« less