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PMID: 3321069 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Identification, purification, and characterization of a mast cell-associated cytolytic factor related to tumor necrosis factor.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 84 ·No. 24 ·1987-12-00 ·Pages 9175-9

Young JD, Liu CC, Butler G, Cohn ZA, Galli SJ

Abstract

The role of mast cells and mast-cell-derived factors in natural cytotoxic reactions was investigated. Cultured and freshly isolated murine mast cells are shown to be cytotoxic to WEHI-164 and YAC-1 targets in 18-hr viability assays but not in 4-hr assays. Here, we describe a cytotoxic factor in murine mast cells that is immunologically related to tumor necrosis factor (TNF). This TNF-like factor lyses WEHI-164 cells with a slow time course requiring 16-20 hr for the lytic reaction to complete. Antibodies specific for human and murine TNF and human lymphotoxin partially block mast cell lysis of WEHI-164 cells. These antibodies react on immunoblots with one major mast cell protein band of 50 kDa. Immunoblot analysis shows this factor in cloned and uncloned cultured mouse mast cells and in mature "connective tissue-type" mast cells freshly purified from rat or mouse peritoneal cavities. The amount of this factor is greatly enhanced in cells that have been stimulated with a combination of phorbol ester/concanavalin A or bacterial lipopolysaccharide. Subcellular fractionation analysis of mast cells with Percoll gradients reveals two pools of TNF-related cytotoxic activity that are associated with free cytosolic material and granule fractions. In contrast to cytotoxic T lymphocytes and natural killer cells, granule-enriched fractions of mast cells do not contain any hemolytic activity. The localization of the TNF-like molecule in mast cell granules may play a strategical role in the rapid delivery of this mediator to the target cell membrane following cell surface stimulation and degranulation.

MeSH Terms
Animals Chromatography, Affinity Cross Reactions Cytotoxicity, Immunologic Cytotoxins/immunology,isolation & purification,metabolism Immunity, Cellular Immunosorbent Techniques Lymphotoxin-alpha Mast Cells/physiology Mice Molecular Weight Subcellular Fractions/analysis Tumor Necrosis Factor-alpha/immunology
Chemicals
Cytotoxins Lymphotoxin-alpha Tumor Necrosis Factor-alpha
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Young J D
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021.
Liu C C
Butler G
Cohn Z A
Galli S J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.84.24.9175
Published
1987-12-00
Pages
9175-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC299715
Subset
IM
Grants
NIAID NIH HHS · AI07012 · United States
NIAID NIH HHS · AI22674 · United States
NCI NIH HHS · CA30198 · United States
External Links
PubMed source DOI: 10.1073/pnas.84.24.9175 PMC Full Text View journal details
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