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Receptor Binding and Activation of Polymorphonuclear Neutrophils by Tumor Necrosis Factor‐Alpha
Author(s) -
Shalaby M.R.,
Palladino M.A.,
Hirabayashi S.E.,
Eessalu T.E.,
Lewis G.D.,
Shepard H.M.,
Aggarwal B.B.
Publication year - 1987
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.41.3.196
Subject(s) - tumor necrosis factor alpha , umbilical vein , internalization , biology , receptor , microbiology and biotechnology , superoxide , endothelial stem cell , granulocyte , binding site , immunology , biochemistry , in vitro , enzyme
The interaction of highly purified recombinant human tumor necrosis factor‐alpha (rTNF‐α) with human polymorphonuclear neutrophils (PMNs) was investigated. Binding of 125 l‐rTNF‐α to PMN reached maximum levels in 30 min at 37°C and in 2 h at 4°C. Scatchard analysis of competitive binding data indicated approximately 6000 receptor sites per cell and a K d of 1.37 nM. Binding data at 37°C indicated a rapid internalization of rTNF‐α. Following this receptor‐mediated interaction, recombinant TNF‐α was found to inhibit the migration of PMNs under agarose and to enhance PMN production of superoxide anion (O ‐ 2 ) in a dose‐dependent manner. Furthermore, rTNF‐α‐activated PMNs caused a marked disruption of human umbilical‐vein‐derived endothelial cell monolayers and caused inhibition of their proliferative activities. These data substantiate the role of TNF‐α as an activator of PMN functions and indicate that PMN/TNF‐α/endothelial cell interactions may play a major role in inflammatory reactions.