HUMAN MONONUCLEAR-CELLS EXPOSED TO STAPHYLOCOCCI RAPIDLY PRODUCE AN INHIBITOR OF NEUTROPHIL CHEMOTAXIS

Serum-free cultures of human peripheral blood mononuclear cells from normal volunteers produce an inhibitor of neutrophil chemotaxis when exposed to heat-killed staphylococci. Human neutrophils were exposed to 100-fold dilutions of supernatants from 6-h cultures, washed repeatedly, and assayed for chemotactic responsiveness with a radiolabeled assay. Dilutions of supernatants from cell cultures exposed to staphylococci resulted in a mean chemotaxis of 856 .+-. 83 cpm (n = 21), while that for medium-treated neutrophils was 1354 .+-. 100 cpm (n = 21, P < 0.001), and supernatants from cultures without staphylococci produced chemotaxis of 1107 .+-. 132 cpm (n = 14, P > 0.05 vs. medium-treated). Fifty-three experiments on tissue from 26 donors showed that after 6 h the mean inhibition (.+-. SE) of chemotaxis at 1:100 dilution was 26.4% .+-. 3.3% (P < 0.001 vs. medium-treated). It was found that the peptidoglycan fraction of the staphylococci was sufficient to induce production of inhibitor by the cooperative action of T cells and monocytes. The inhibitor is a protein with a MW of 30-45 kilodaltons. It is not toxic to the neutrophils and does not affect secretion, adhesion, phagocytosis, or the ability to kill Staphylococcus aureus. This potent inhibitor of neutrophil chemotaxis may play a role in the modulation of neutrophil function during bacterial infections.