Biological and kinetic characterization of recombinant human macrophage inflammatory peptides 2 alpha and beta and comparison with the neutrophil activating peptide 2 and interleukin 8.

We examined the biological and kinetic characteristics of two new members of the intercrine family of cytokines. Human macrophage inflammatory peptides 2 alpha and beta (huMIP-2 alpha and beta) were compared to human interleukin 8 (huIL-8), neutrophil activating peptide 2 (huNAP-2), and N-formyl-L-methionyl-L-phenylalanine (fMLP). The huMIP-2 peptides were the least potent cytokine tested in triggering neutrophil degranulation. They were also less potent neutrophil chemotaxins than fMLP or huIL-8. However, they were more effective than NAP-2 in stimulating chemotaxis of neutrophils. The binding studies showed that huMIP-2 peptides could interact with specific receptors on human blood neutrophils. Moreover, huMIP-2 peptides competed for up to 60% of the huIL-8 binding sites on neutrophils whereas huIL-8 competed for almost 100% of either of the huMIP-2 peptide binding sites. These data suggest the huMIP-2 peptides have little or no affinity for 40% of the huIL-8 receptors. In addition, detectable amounts of mRNA for huMIP-2 alpha were found in samples from human alveolar macrophages stimulated with Staphylococcus aureus, toxic shock syndrome toxin-1 (TSST), but not in samples stimulated with S. aureus enterotoxin A (SEA) or Escherichia coli endotoxin (lipopolysaccharide = LPS). In conclusion, huMIP-2 alpha and beta are weak neutrophil stimulating agents, which may increase inflammation in diseases such as toxic shock syndrome.