Modulation of human neutrophil function by fibronectin degradation products isolated from cryoglobulins.
The proteolytic fragments of native fibronectin (cryopeptides) complexed to pathological immunoglobulins in cryoglobulins were isolated from the serum of six different patients. Two peptides of 117,000 daltons and 70,000 daltons were purified and characterized by N-terminal amino acid sequencing. The priming effect of the mixture of these two peptides, referred to as cryopeptides, on neutrophil functions, namely the respiratory burst, exocytosis, and Ca2+ release, was investigated. Cryopeptides and cryoglobulins assayed separately did not increase neutrophil respiration or cytosol free calcium concentration; however, both of them induced granule enzyme secretion. Sequential exposure of neutrophils to either cryopeptides or the respective cryoglobulins, and then to N-formyl-methionyl-leucyl-phenylalanine or serum opsonized zymosan, resulted in a synergistic stimulation of O2 uptake compared to the effect of N-formyl-peptides or opsonized zymosan tested separately; Ca2+ release was significantly enhanced by the pretreatment of neutrophils with cryopeptides. These data suggest that cryopeptides and cryoglobulins may play a role in host defense against bacterial infections through neutrophil activation.
Morel
F
F
Laboratoire d'Enzymologie, CHRU, Grenoble, France.
Cholley
L C
LC
Dianoux
A C
AC
Renversez
J C
JC
Anthony
D
D
Revol
C
C
Boulay
F
F
Gagnon
J
J
Vignais
P V
PV
D000595:Amino Acid Sequence; D002118:Calcium / Q000097:blood*; D002469:Cell Separation; D003450:Cryoglobulins / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology; D005353:Fibronectins / Q000097:blood*; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D007962:Leukocytes / Q000166:cytology; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D010446:Peptide Fragments / Q000097:blood* / Q000302:isolation & purification; D016897:Respiratory Burst / Q000502:physiology
D003450:Cryoglobulins; D005353:Fibronectins; D010446:Peptide Fragments; D006861:Hydrogen Peroxide; D010100:Oxygen; D002118:Calcium