Inhibition of neutrophil and natural killer cell function by human seminal fluid acid phosphatase.
The major acid phosphatase of human seminal fluid was purified to homogeneity by chromatography on Sephadex G-150, and DEAE-Sephadex, and by isoelectric focusing (pI, 4.3). This purified preparation of seminal fluid acid phosphatase blocked superoxide anion production by neutrophils stimulated with fMet-Leu-Phe (fMLP) by 50%. The phosphatase also hydrolysed myo-inositol 1,4,5-trisphosphate (IP3) in vitro, an intracellular second messenger which releases Ca2+ from intracellular pools, at nearly one-third the rate at which the nonphysiologic substrate 4-methylumbelliferylphosphate (MUP) was cleaved. In contrast, two phosphoinositide lipids, namely phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-monophosphate, were poor phosphatase substrates. Following fMLP stimulation of [3H]inositol-labeled neutrophils, the quantity of IP3 produced by phosphatase-treated cells was reduced by 69%. These results indicate that the human seminal fluid acid phosphatase may compromise the neutrophil's microbicidal response to the organism by hydrolyzing a second messenger (IP3) which is directly involved in the regulation of intracellular Ca2+ concentrations. The seminal fluid phosphatase also inhibited by 85% the ability of murine natural killer (NK) cells to inactivate target cells.
Mukhopadhyay
N K
NK
Department of Microbiology, University of Pittsburgh, School of Medicine, PA 15261.
Saha
A K
AK
Smith
W
W
Dowling
J N
JN
Hiserodt
J
J
Glew
R H
RH
D000135:Acid Phosphatase / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002845:Chromatography; D006801:Humans; D006868:Hydrolysis; D006923:Hymecromone / Q000031:analogs & derivatives / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism; D007525:Isoelectric Focusing; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D012661:Semen / Q000201:enzymology*; D013481:Superoxides / Q000378:metabolism
D007295:Inositol Phosphates; D013481:Superoxides; C005359:4-methylumbelliferyl phosphate; D006923:Hymecromone; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015544:Inositol 1,4,5-Trisphosphate; D000135:Acid Phosphatase