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Lymphotoxin Induces Secretion of Granule Proteins From Adherent Neutrophils: Possible Role of Intracellular Free Calcium
Author(s) -
Richter Johan
Publication year - 1990
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.47.6.506
Subject(s) - secretion , biology , lymphotoxin , granule (geology) , microbiology and biotechnology , intracellular , calcium in biology , calcium , immunology , tumor necrosis factor alpha , biochemistry , medicine , paleontology
Lymphotoxin (LT) can activate human neutrophils. Using a hemolytic plaque assay to detect secretion of lactoferrin and myeloperoxidase (MPO) from single adherent neutrophils, we showed that LT induced secretion from both primary and secondary granules. Incubation of cells with cytochalasin B was required for MPO secretion, and it enhanced lactoferrin secretion. Pertussis toxin, which blocks a G‐protein in the plasma membrane, inhibited LT‐induced exocytosis of MPO, but not of lactoferrin. Incubation with LT did not induce any detectable changes of the cytoplasmic free [Ca 2+ ] in neutrophils. On the other hand, secretion of granule proteins from adherent neutrophils in response to LT was blocked by loading neutrophils with quin‐2 in order to increase the intracellular calcium buffering capacity. This was achieved at a concentration of quin‐2, at which the secretion induced by the phorbol ester PMA and the chemotactic peptide FMLP was unaffected. Trifluoroperazine (TFP), a dual protein kinase C and calmodulin inhibitor, significantly inhibited the LT‐mediated secretion of lactoferrin from adherent granulocytes. The PMA effect was unaltered by TFP under these conditions, suggesting that the inhibitory effect was on a calcium‐calmodulin dependent step. The secretion induced by TNF and GM‐CSF was also blocked by buffering changes in the intracellular ICa 2+ ] and inhibited to a similar extent by TFP. Our results suggest that calmodulin and minute changes in the cytoplasmic free [Ca 2+ ] may be involved in a common signal transduction pathway engaged in activation of adherent neutrophils by several cytokines.