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.
Department of Biochemistry, University of Texas Health Center at Tyler 75710.
A
A
Kurdowska
A B
AB
Cohen
F K
FK
Carr
M D
MD
Stevens
E J
EJ
Miller
G
G
Mullenbach
P
P
Tekamp-Olson
D001427:Bacterial Toxins; D001483:Base Sequence; D001665:Binding Sites; D015139:Blotting, Southern; D002478:Cells, Cultured; D054426:Chemokine CXCL2; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology*; D017931:DNA Primers; D004768:Enterotoxins / Q000494:pharmacology; D004926:Escherichia coli; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D019272:Leukocyte Elastase; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D015846:Monokines / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D010196:Pancreatic Elastase / Q000097:blood*; D009195:Peroxidase / Q000097:blood*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013211:Staphylococcus aureus; D018089:Superantigens
D001427:Bacterial Toxins; D054426:Chemokine CXCL2; D016207:Cytokines; D017931:DNA Primers; D004768:Enterotoxins; D016209:Interleukin-8; D008070:Lipopolysaccharides; D015846:Monokines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C026066:enterotoxin A, Staphylococcal; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009195:Peroxidase; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase