ACTIVATION OF THE NEUTROPHIL BACTERICIDAL ACTIVITY FOR NONTYPABLE HAEMOPHILUS-INFLUENZAE BY TUMOR-NECROSIS-FACTOR AND LYMPHOTOXIN

Previous studies have suggested that, in vivo, activated T lymphocytes and neutrophils are important in immunity to nontypable Haemophilus i nfluenzae. We now extend this work by showing that neutrophils pretrea ted with products of activated T lymphocytes or activated macrophages show significantly enhanced killing of nontypable H. influenzae. Lymph otoxin, a product of activated T lymphocytes, significantly enhanced t he neutrophil-mediated killing of nontypable H. influenzae, and tumor necrosis factor, produced by activated T lymphocytes as well as macrop hages stimulated by activated T lymphocytes, also significantly increa sed the bactericidal activity of neutrophils. These cytokine-induced e ffects were seen with short pretreatment times of neutrophils and were maximal by 30 min. The killing of H. influenzae by neutrophils requir ed the presence of heat-labile opsonins. In the absence of these opson ins, both tumor necrosis factor and lymphotoxin were unable to promote the killing of the bacteria by neutrophils. Furthermore, the results showed that tumor necrosis factor-primed neutrophils displayed signifi cantly increased expression of CR3 and CR4 that was associated with in creased phagocytosis of complement-opsonized nontypable H. influenzae. These cytokines may play an important role in immunity toward nontypa ble H. influenzae by stimulating neutrophil bactericidal activity.