The local role of tumor necrosis factor alpha in the modulation of neutrophil function at sites of inflammation
J. Yee and N. V. Christou
Department of Surgery, Royal Victoria Hospital, McGill University, Montreal, Quebec.
OBJECTIVE: To examine the hypothesis that tumor necrosis factor alpha
(TNF-alpha) is an important local modulator of neutrophil function in the
inflammatory microenvironment. DESIGN: In vitro studies of host defense.
PATIENTS: A volunteer sample of healthy subjects. INTERVENTION: Exudative
neutrophils were collected from skin-blister chambers and functionally
compared with blood neutrophils. METHODS: Tumor necrosis factor alpha
levels at sites of inflammation and neutrophil exudation were determined
and compared with serum concentrations. Flow cytometry was used to evaluate
neutrophil microbicidal activity and
N-formyl-methionyl-leucyl-phenylalanine-induced changes in intracellular
calcium and superoxide production. In vitro TNF-alpha was used to evaluate
the nature and dose response of TNF-alpha-induced changes in neutrophil
function. RESULTS: Exudative neutrophils have an increased responsiveness
to subsequent N-formyl-methionyl-leucyl-phenylalanine stimulation, as
determined by changes in intracellular calcium. Microbicidal activity and
superoxide production are also up-regulated compared with circulating
neutrophils. The exudative microenvironment contains TNF-alpha at local
levels that are capable of significantly enhancing neutrophil host defense.
CONCLUSIONS: Tumor necrosis factor alpha may serve to enhance neutrophil
function at sites of inflammation. Neutrophils become more cytotoxic and
have an enhanced ability to respond to weak environmental signals.
