A SYNTHETIC PEPTIDE WHICH SPECIFICALLY INHIBITS HEAT-TREATED INTERLEUKIN-8 BINDING AND CHEMOTAXIS FOR NEUTROPHILS

Interleukin-8 (IL-8) is a peptide which is secreted by stimulated huma n monocytes and which is chemotactic for human neutrophils. We synthes ized three overlapping peptides spanning the amino-terminal region of the IL-8 sequence. None of the peptides retained the chemotactic activ ity of the native molecule. One of the peptides, IL-8((3-25)), inhibit ed the neutrophil chemotactic activity of recombinant IL-8 (rIL-8) whi ch had been preheated to 40 degrees C but did not reduce neutrophil ch emokinesis, or the chemotactic activity of unheated rIL-8, FMLP, C5a o r LTB(4). Interleukin-8 exhibited similar binding kinetics and chemota xis for neutrophils regardless of whether it had been pretreated at 40 degrees C. In addition, IL-8((3-25)) was also able to decrease the bi nding of preheated IL-8 to neutrophils. IL-8((3-25)), which can self-a ssociate, binds directly to receptors on the neutrophil. The data sugg est that heat-treated, but not untreated, IL-8 causes the IL-8((3-25)) multimers to disaggregate, allowing the monomeric peptide to directly bind to the IL-8 receptor and thus inhibiting IL-8/receptor binding.