Bactericidal capacity of phorbol myristate acetate-treated human polymorphonuclear leukocytes

Publisher Website
Google Scholar
Abstract
The functional capacity of phorbol myristate acetate- (PMA)-treated human polymorphonuclear leukocytes was studied. PMA induced exocytosis of lactoferrin, the specific granule marker, but not of myeloperoxidase, the azurophil granule marker. This phenomenon was demonstrated biochemically and with fluorescent antibody conjugates. PMA-treated neutrophils contained virtually no specific granules when viewed by EM. Separation of the granule classes by linear sucrose density gradient centrifugation revealed the loss, from PMA-treated neutrophils, of lactoferrin and the specific granule band usually resolved from normal neutrophils. Cells treated with PMA appeared to retain those functions normally associated with intraleukocytic microbicidal action. The hexose monophosphate shunt activated by phogocytic challenge was present in PMA-treated neutrophils. As demonstrated by EM, the azurophil granules of these cells appeared intact and they retained the capacity for degranulation with translocation of myeloperoxidase to the site of phagocytized Escherichia coli. The PMA-treated neutrophils also remained capable of degrading the ingested microorganisms. PMA-treated neutrophils exhibited a decrease in phagocytic ability at all levels of bacterial challenge. In the presence of a high multiplicity of bacteria they demonstrated an impairment in killing. These same cells were able to kill low multiplicities of E. coli as well as control cells. Apparently the loss of the specific granules, plus other undefined PMA-induced alterations, impaired neither the viability of these neutrophils nor their killing ability in the presence of a modest phagocytic challenge.