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

• Published in: Cytokine (Philadelphia, Pa.) Vol. 6; no. 2; pp. 124 - 134
• Main Authors: Kurdowska, Anna, Cohen, Allen B., Carr, Ferdicia K., Stevens, Michael D., Miller, Edmund J., Mullenbach, Guy, Tekamp-Olson, Patricia
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.1994
• Subjects: Bacterial Toxins; Base Sequence; Binding Sites; Blotting, Southern; Cells, Cultured; Chemokine CXCL2; Chemotaxis; Chemotaxis, Leukocyte - drug effects; Cytokine; Cytokines - biosynthesis; Cytokines - metabolism; Cytokines - pharmacology; DNA Primers; Enterotoxins - pharmacology; Escherichia coli; Humans; Inflammation; Intercrine; Interleukin-8 - metabolism; Interleukin-8 - pharmacology; Kinetics; Leukocyte Elastase; Lipopolysaccharides - pharmacology; Macrophage Inflammatory Peptide; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - physiology; Molecular Sequence Data; Monokines - biosynthesis; Monokines - metabolism; Monokines - pharmacology; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Neutrophils - drug effects; Neutrophils - enzymology; Neutrophils - physiology; Pancreatic Elastase - blood; Peroxidase - blood; Polymerase Chain Reaction; Recombinant Proteins - pharmacology; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; Staphylococcus aureus; Superantigens; Intercrine; Inflammation; Chemotaxis; Macrophage Inflammatory Peptide; Cytokine
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/1043-4666(94)90033-7

We examined the biological and kinetic characteristics of two new members of the intercrine family of cytokines. Human macrophage inflammatory peptides 2 α and β (huMIP-2α and β) were compared to human interleukin 8 (huIL-8), neutrophil activating peptide 2 (huNAP-2), and N-formyl-L-methionyl-L-leucyl-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-2α 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-2α and β are weak neutrophil stimulating agents, which may increase inflammation in diseases such as toxic shock syndrome.