Role of calpains and kininogens in inflammation.
Neutrophil chemotactic activity was found in the autodigest of calcium dependent cysteine proteinase (calpain) I purified from human erythrocytes, an active peptide was isolated, and its structure was determined. It was an N-acetyl nonapeptide with the sequence: N-acetyl Ser-Glu-Glu-Ile-Ile-Thr-Pro-Val-Tyr. This peptide was identical with the N-terminal amino acid sequence of the large subunit of calpain I deduced from cDNA sequence, except that the peptide was lacking a methionine residue and was acetylated at the N-terminus. A number of N-acetyl peptides with N-terminal amino acid sequences of large and small subunits of calpains I and II were synthesized and their chemotactic activity was estimated. In addition to the N-acetyl nonapeptide from calpain I large subunit, several peptides of different lengths from the small subunit showed dose-dependent migrations of neutrophils. They include N-acetyl tetra, hepta, octa, nona and larger size peptides. Further, it was also revealed that when calpain was incubated with high molecular weight (HMW) or low molecular weight (LMW) kininogen, kinin liberation occurred with simultaneous inhibition of calpains by kininogens. These data suggest that chemical mediators generated from the calpain-kininogen system may participate in migration and accumulation of neutrophils to the inflammatory locus.
Sasaki
M
M
Department of Biochemistry, Nagoya City University Medical School, Japan.
Kunimatsu
M
M
Ohkubo
I
I
D000595:Amino Acid Sequence; D000818:Animals; D002154:Calpain / Q000276:immunology* / Q000302:isolation & purification; D002630:Chemotactic Factors / Q000276:immunology / Q000302:isolation & purification; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004912:Erythrocytes / Q000737:chemistry; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D007704:Kininogens / Q000276:immunology*; D007705:Kinins / Q000378:metabolism; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology
D002630:Chemotactic Factors; D007704:Kininogens; D007705:Kinins; D009842:Oligopeptides; D002154:Calpain