Monocyte-chemotactic activity of defensins from human neutrophils.
We investigated the monocyte-chemotactic activity of fractionated extracts of human neutrophil granules. Monocyte-chemotactic activity was found predominantly in the defensin-containing fraction of the neutrophil granules. Purified preparations of each of the three human defensins (HNP-1, HNP-2, HNP-3) were then tested. HNP-1 demonstrated significant chemotactic activity for monocytes: Peak activity was seen at HNP-1 concentrations of 5 X 10(-9) M and was 49 +/- 20% (mean +/- SE, n = 9) of that elicited by 10(-8) M FMLP. HNP-2 (peak activity at 5 X 10(-9) M) was somewhat less active, yielding 19 +/- 10% (n = 11). HNP-3 failed to demonstrate chemotactic activity. Checkerboard analysis of monocyte response to HNP-1 and HNP-2 confirmed that their activity was chemotactic rather than chemokinetic. Neutrophils demonstrated a low level of response to defensins but this reaction was primarily chemokinetic. Defensins may play a role in the recruitment of monocytes by neutrophils into inflammatory sites.
Territo
M C
MC
Department of Medicine, University of California, Los Angeles 90024.
Ganz
T
T
Selsted
M E
ME
Lehrer
R
R
D001798:Blood Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003594:Cytoplasmic Granules / Q000032:analysis*; D006801:Humans; D009000:Monocytes / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000648:ultrastructure*; D023084:alpha-Defensins
D001798:Blood Proteins; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; D009240:N-Formylmethionine Leucyl-Phenylalanine