INTERLEUKIN-8 (IL-8), MELANOMA GROWTH-STIMULATORY ACTIVITY, AND NEUTROPHIL-ACTIVATING PEPTIDE SELECTIVELY MEDIATE PRIMING OF THE NEUTROPHILNADPH OXIDASE THROUGH THE TYPE-A OR TYPE-B IL-8 RECEPTOR

The capacity of neutrophils to generate superoxide (O-2(T)) can be enh anced by prior exposure to ''priming'' agents such as interleukin-8 (I L-8), melanoma growth-stimulatory activity (MGSA), and neutrophil-acti vating peptide (ENA-78). The biological effects of these chemokines ar e mediated by at least two distinct receptors: type A (IL-8-RA) and ty pe B (IL-8-RB). Using neutralizing monoclonal antibodies to ILS-RA and IL-8-RB, we have investigated the contribution each receptor makes to the priming response, Preincubation with IL-8, MGSA, or ENA-78 enhanc ed the ability of neutrophils to generate O-2(T) following stimulation with the bacterial peptide formyl-Met-Leu-Phe. The priming effect of IL-8 was eliminated by an anti-IL-8 monoclonal antibody (mAb) that is known to bind IL-8 with high affinity and prevent receptor occupancy. Incubation of neutrophils with a neutralizing mAb specific for IL-8-RA blocked IL-8-induced priming but had no effect on priming by MGSA or ENA-78. In contrast, treatment with a neutralizing mAb specific for IL -8-RB faded to inhibit the priming effect of IL-8 but blocked both MGS A and ENA-78-induced priming. These observations indicate that the pri ming effect of IL-8 on the neutrophil respiratory burst is predominant ly mediated via IL-8-RA whereas priming by MGSA and ENA-78 is mediated by IL-8-RB.