3 NONCONTIGUOUS PEPTIDES COMPRISE BINDING-SITES ON HIGH-MOLECULAR-WEIGHT KININOGEN TO NEUTROPHILS

The binding of high-molecular-weight kininogen (HX) to neutrophils (po lymorphonuclear leukocytes, PMN) is required for the stimulation of ag gregation and degranulation by human plasma kallikrein as well as the displacement of fibrinogen from this cell surface. The putative recept or for HK is the leukocyte integrin alpha(M)beta(2), and domains 3 (D3 ) and 5 (D5) of HK form its binding site. To further map the binding s ites on HK for PMN, we used D3 recombinant exon products and designed peptides from D3 and D5. In D3, a heptapeptide, Leu(271)-Ala(277) from exon 7 product, and a peptide, Cys(333)-Cys(352), from exon 9 product can inhibit binding of kininogen to PMN. Two contiguous peptides from D5 in the histidine-glycine-rich region, Gly(442)-Lys(458) and Phe(45 9)-Lys(478), each inhibit the binding of HK to PMN. This study has thu s delineated three noncontiguous surface-oriented sequences on HK, whi ch together comprise all or most of the binding site for human PMN.