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1,25‐Dihydroxyvitamin D 3 Induces Responsiveness to the Chemotactic Peptide f‐Met‐Leu‐Phe in the Human Monocytic Line U937: Dissociation Between Calcium and Oxidative Metabolic Responses
Author(s) -
Polla Barbara S.,
Werlen Guy,
Clerget Michel,
Pittet Didier,
Rossier Michel F.,
Capponi Alessandro M.
Publication year - 1989
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.45.5.381
Subject(s) - u937 cell , superoxide , chemotaxis , respiratory burst , biology , inositol , nadph oxidase , receptor , inositol phosphate , pertussis toxin , n formylmethionine leucyl phenylalanine , biochemistry , calcium , biophysics , endocrinology , medicine , reactive oxygen species , g protein , enzyme , in vitro
In the human premonocytic line U937, 1,25‐dihydroxyvitamin D 3 (1,25‐(OH) 2 D 3 ) induces a functional NADPH oxidase, that is responsive to both phorbol esters and opsonized zymosan. The chemotactic peptide f‐Met‐Leu‐Phe (fMLP) did not. however, induce superoxide generation by these cells. This was not due to the absence of receptors for fMLP. Although there was no significant binding of [ 3 H]‐fMLP to undifferentiated U937 cells, preincubation with 1,25‐(OH) 2 D 3 induced expression of specific and saturable binding sites. Moreover, fMLP induced a rapid and reversible rise in cytosolic free Ca 1+ concentration ([Ca 2+ ] i ) in 1,25‐(OH) 2 D 3 ‐treated U937 cells, but not in control or 24,25‐dihydroxyvitamin D 3 (24,25‐(OH) s D 3 )‐treated cells. This [Ca 2+ ] i response was dependent on concentrations of both fMLP and 1,25‐(OH) 2 D 3 and was observed at physiologic concentrations of the hormone (25 pM). The rise in [Ca 2+ ] i induced by fMLP in 1,25‐(OH) 2 D 3 ‐treated U937 cells was blocked by pertussis toxin and presumably mediated by inositol (1,4.5)‐trisphosphate generation. These results indicate that in U937 cells differentiated with 1,25‐(OH) 2 D 3 , inositol phosphate‐mediated [Ca 2+ ] i responses to fMLP are uncoupled from NADPH oxidase activation.