TI  - Differential mechanisms of recognition and activation of <prot>interleukin-8</prot>c
      receptor subtypes.
PG  - 11768-72
AB  - We have probed an epitope sequence (His18-Pro19-Lys20-Phe21) in
     <prot>interleukin-8</prot> (<prot>IL-8</prot>) by site-directed mutagenesis. This work shows that
      single and double Ala substitutions of His18 and Phe21 in <prot>IL-8</prot> reduced up
      to 77-fold the binding affinity to <prot><prot>IL-8</prot> receptor subtypes A</prot>(<prot>CXCR1</prot>) and B
       (<prot>CXCR2</prot>) and to the  <prot>Duffy antigen</prot> . These Ala mutants triggered neutrophil
      degranulation and induced calcium responses mediated by <prot>CXCR1</prot> and <prot>CXCR2</prot>.
      Single Asp or Ser substitutions, H18D, F21D, F21S, and double
      substitutions, H18A/F21D, H18A/F21S, and H18D/F21D, reduced up to 431-fold
      the binding affinity to <prot>CXCR1</prot>, <prot>CXCR2</prot>, and the <prot>Duffy antigen</prot>.
      Interestingly, double mutants with charged residue substitutions failed to
      trigger degranulation or to induce wild-type calcium responses mediated by
      <prot>CXCR1</prot>. Except for the H18A and F21A mutants, all other <prot>IL-8</prot> mutants failed
      to induce superoxide production in neutrophils. This study demonstrates
      that    <prot>IL-8</prot>    recognizes and activates  <prot>CXCR1</prot> ,  <prot>CXCR2</prot> , and the  <prot>Duffy antigen</prot>  by
      distinct mechanisms.
AD  - Department of Physiology and Biophysics and Sealy Center for Molecular
