The local role of tumor necrosis factor alpha in the modulation of neutrophil function at sites of inflammation.
OBJECTIVE
To examine the hypothesis that tumor necrosis factor alpha (TNF-alpha) is an important local modulator of neutrophil function in the inflammatory microenvironment.


METHODS
In vitro studies of host defense.


METHODS
A volunteer sample of healthy subjects.


METHODS
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.
Yee
J
J
Department of Surgery, Royal Victoria Hospital, McGill University, Montréal, Quebec.
Christou
N V
NV
D001770:Blood Bactericidal Activity; D015220:Calcium Channels / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005122:Exudates and Transudates / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology*; D007424:Intracellular Fluid / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology*; D013481:Superoxides; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology*
D015220:Calcium Channels; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine