Establishment of an immature mast cell line from a patient with mast cell leukemia

Butterfield, Joseph H.; Weiler, Deborah A.; Dewald, Gordon W.; Gleich, Gerald J.

doi:10.1016/0145-2126(88)90050-1

Cited by 685 publications

(527 citation statements)

References 38 publications

Supporting

Mentioning

521

Contrasting

Unclassified

Order By: Relevance

“…The human mast cell line HMC-1 was kindly provided by Dr Butterfield [18]. The more differentiated subclone 5C6 was derived from the original HMC-1 cell line by limiting dilution [19].…”

Section: Methodsmentioning

confidence: 99%

Human Leukaemic (HMC‐1) and Normal Skin Mast Cells Express β2‐Integrins: Characterization of β2‐Integrins and ICAM‐1 on HMC‐1 Cells

et al. 1997

View full text Add to dashboard Cite

Weber S, Babina M, Feller G, Henz BM. Human Leukaemic (HMC-1) and Normal Skin Mast Cells Express b2-Integrins: Characterization of b2-Integrins and ICAM-1on HMC-1 Cells. Scand J Immunol 1997;45:471-481 Mast cells are bone marrow-derived, ubiquitous connective tissue resident cells. However, their mechanisms of migration, the distribution of immature and mature cells and their interaction with other inflammatory cells are largely unclarified. Possibly, b2-integrins play an important role in these processes. In the present investigation, the authors studied the expression and regulation of the b2-integrins LFA-1 (CD11a/CD18), Mac-1 (CD11b/CD18), p150,95 (CD11c/CD18) and of the LFA-1/Mac-1 counter-receptor intercellular adhesion molecule-1 (ICAM-1; CD54) on leukaemic (HMC-1 cell subclone 5C6) and on normal mature human skin mast cells. The HMC-1 cells clearly expressed CD11a, CD18 and CD54, while expression of CD11b and CD11c was low. The apparent molecular weights were 180 kDa (CD11a), 95 kDa (CD18) and 90 kDa (CD54) as determined by Western blot analysis. Phorbol myristate acetate (PMA) induced a time-and dose-dependent up-regulation of CD11a, CD11b, CD11c, CD18 and CD54 that was inhibited by cycloheximide, suggesting a dependence on de novo protein synthesis. Enhanced expression of CD11a, CD11b, CD11c and CD18 could also be confirmed at the gene level as demonstrated by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Increased expression of LFA-1/ICAM-1 in response to PMA was accompanied by strong enhancement of homotypic cell aggregation, suggesting that newly synthesized LFA-1/ICAM-1 is functionally active. In order to determine a physiologically relevant way of mast cell b2-integrin modulation, several cytokines and chemotactic mediators (interleukin-4, IL-4; nerve growth factor b, NGFb; C5a; and leukotriene B4, LTB4) were tested for their influence on adhesion molecule cell surface density. Only LTB4 was shown specifically to up-regulate CD11a and CD18, but not CD11b or CD11c. The presence of CD11a, CD11c and CD18 could be confirmed on a low percentage of normal skin mast cells by immunofluorescence, using a double staining technique. In comparison to normal skin, a significantly higher percentage of CD18 þ mast cells was found in inflammatory dermatoses such as psoriasis vulgaris, atopic dermatitis and lichen planus. Therefore, mast cell b2-integrins possibly play an important role during homing of immature mast cells as well as during the interaction of activated mast cells with other inflammatory cells.

show abstract

“…The human mast cell line HMC-1 was kindly provided by Dr Butterfield [18]. The more differentiated subclone 5C6 was derived from the original HMC-1 cell line by limiting dilution [19].…”

Section: Methodsmentioning

confidence: 99%

Human Leukaemic (HMC‐1) and Normal Skin Mast Cells Express β2‐Integrins: Characterization of β2‐Integrins and ICAM‐1 on HMC‐1 Cells

et al. 1997

View full text Add to dashboard Cite

show abstract

“…Two subclones of the human MCL line HMC-1 were used, HMC-1.1 harbouring KIT V560G, and HMC-1.2 harbouring KIT V560G and KIT D816V (21,26,40). A detailed description of cell lines is provided in the Supplement.…”

Section: Cell Linesmentioning

confidence: 99%

Target interaction profiling of midostaurin and its metabolites in neoplastic mast cells predicts distinct effects on activation and growth

et al. 2015

View full text Add to dashboard Cite

Proteomic-based drug testing is an emerging approach to establish the clinical value and antineoplastic potential of multi-kinase inhibitors. The multikinase inhibitor midostaurin (PKC412) is a promising new agent used to treat patients with advanced systemic mastocytosis (SM). We examined the target interaction-profiles and the mast cell (MC)-targeting effects of two pharmacologically relevant midostaurin metabolites, CGP52421 and CGP62221. All three compounds, midostaurin and the two metabolites, suppressed IgE-dependent histamine secretion in basophils and MC with reasonable IC 50 values. Midostaurin and CGP62221 also produced growth-inhibition and dephosphorylation of KIT in the MC leukemia cell line HMC-1.2, whereas the second metabolite, CGP52421, that accumulates in vivo, showed no substantial effects.Chemical proteomic profiling and drug-competition experiments revealed that midostaurin interacts with KIT and several additional kinase-targets. The key downstream-regulator FES was recognized by midostaurin and CGP62221, but not by CGP52421 in MC lysates, whereas the IgEreceptor-downstream target SYK was recognized by both metabolites. Together, our data show that the clinically relevant midostaurin metabolite CGP52421 inhibits IgE-dependent histamine release, but is a weak inhibitor of MC proliferation which may have clinical implications and may explain why mediator-related symptoms improve in SM patients even when disease progression occurs.

show abstract

“…The mast cell line HMC-1 was kindly provided by Joseph H. Butterfield (Mayo Clinic, Rochester, MN). 33 Two subclones were used: HMC-1.1, harboring KIT V560G but not KIT D816V 34 (referred to as KIT D816V Ϫ HMC-1 cells), and HMC-1.2, harboring KIT V560G as well as KIT D816V 33,34 (referred to as KIT D816V ϩ HMC-1 cells). HMC-1 cells were cultured in Iscove's modified Dulbecco's medium with 10% FCS.…”

Section: Cells and Cell Culturementioning

confidence: 99%

Identification of Oncostatin M as a STAT5-Dependent Mediator of Bone Marrow Remodeling in KIT D816V-Positive Systemic Mastocytosis

Hoermann

Cerny-Reiterer

Perné

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Systemic mastocytosis is a neoplastic disease of mast cells harboring the activating KIT mutation D816V. In most patients, mast cell infiltration in the bone marrow is accompanied by marked microenvironment alterations, including increased angiogenesis, osteosclerosis, and sometimes fibrosis. Little is known about the mast cell-derived molecules contributing to these bone marrow alterations. We show here that neoplastic mast cells in patients with systemic mastocytosis express oncostatin M (OSM), a profibrogenic and angiogenic modulator. To study the regulation of OSM expression, KIT D816V was inducibly expressed in Ba/F3 cells and was found to up-regulate OSM mRNA and protein levels, suggesting that OSM is a KIT D816V-dependent mediator. Correspondingly, KIT D816V ؉ HMC-1.

show abstract

Establishment of an immature mast cell line from a patient with mast cell leukemia

Cited by 685 publications

References 38 publications

Human Leukaemic (HMC‐1) and Normal Skin Mast Cells Express β2‐Integrins: Characterization of β2‐Integrins and ICAM‐1 on HMC‐1 Cells

Human Leukaemic (HMC‐1) and Normal Skin Mast Cells Express β2‐Integrins: Characterization of β2‐Integrins and ICAM‐1 on HMC‐1 Cells

Target interaction profiling of midostaurin and its metabolites in neoplastic mast cells predicts distinct effects on activation and growth

Identification of Oncostatin M as a STAT5-Dependent Mediator of Bone Marrow Remodeling in KIT D816V-Positive Systemic Mastocytosis

Contact Info

Product

Resources

About