Interleukin-8 (IL-8), melanoma growth-stimulatory activity, and neutrophil-activating peptide selectively mediate priming of the neutrophil NADPH oxidase through the type A or type B IL-8 receptor.
The capacity of neutrophils to generate superoxide (O-2) can be enhanced by prior exposure to "priming" agents such as interleukin-8 (IL-8), melanoma growth-stimulatory activity (MGSA), and neutrophil-activating peptide (ENA-78). The biological effects of these chemokines are mediated by at least two distinct receptors: type A (IL-8-RA) and type B (IL-8-RB). Using neutralizing monoclonal antibodies to IL-8-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 enhanced the ability of neutrophils to generate O-2 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 failed to inhibit the priming effect of IL-8 but blocked both MGSA and ENA-78-induced priming. These observations indicate that the priming effect of IL-8 on the neutrophil respiratory burst is predominantly mediated via IL-8-RA, whereas priming by MGSA and ENA-78 is mediated by IL-8-RB.
Green
S P
SP
Department of Immunology, Genentech, Inc., South San Francisco, California 94080, USA.
Chuntharapai
A
A
Curnutte
J T
JT
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000031:analogs & derivatives / Q000494:pharmacology*; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019255:NADPH Oxidases / Q000097:blood*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D018123:Receptors, Interleukin / Q000276:immunology / Q000502:physiology; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D013481:Superoxides / Q000097:blood
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C475829:CXCL1 protein, human; C486263:CXCL5 protein, human; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019255:NADPH Oxidases