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 human monocytes and which is chemotactic for human neutrophils. We synthesized three overlapping peptides spanning the amino-terminal region of the IL-8 sequence. None of the peptides retained the chemotactic activity of the native molecule. One of the peptides, IL-8(3-25), inhibited the neutrophil chemotactic activity of recombinant IL-8 (rIL-8) which had been preheated to 40 degrees C but did not reduce neutrophil chemokinesis, or the chemotactic activity of unheated rIL-8, FMLP, C5a or LTB4. Interleukin-8 exhibited similar binding kinetics and chemotaxis 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 binding of preheated IL-8 to neutrophils. IL-8(3-25), which can self-associate, binds directly to receptors on the neutrophil. The data suggest 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.
Department of Biochemistry, University of Texas Health Science Center at Tyler 75710.
E J
EJ
Miller
A
A
Kurdowska
S
S
Nagao
F K
FK
Carr
S
S
Hayashi
M A
MA
Atkinson
A B
AB
Cohen
D000595:Amino Acid Sequence; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D006358:Hot Temperature; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet
D016209:Interleukin-8; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D010455:Peptides; C088035:interleukin-8 (3-25)