Jf. Sweeney et al., AUTOCRINE PARACRINE MODULATION OF POLYMORPHONUCLEAR LEUKOCYTE SURVIVAL AFTER EXPOSURE TO CANDIDA-ALBICANS/, Shock, 9(2), 1998, pp. 146-152
Citations number
47
Categorie Soggetti
Peripheal Vascular Diseas","Emergency Medicine & Critical Care",Hematology
Polymorphonuclear leukocytes (PMN) play a central role in the host res
ponse to injury and infection. These terminally differentiated phagocy
tes have a limited life span, after which they undergo spontaneous apo
ptosis. PMN life span can be significantly prolonged by several natura
lly occurring cytokines, and PMN are now known to be capable of cytoki
ne production in response to various antigenic stimuli. These facts su
ggest the possibility that PMN possess an autocrine/paracrine mechanis
m for the control of their own survival. The present study was underta
ken to test this hypothesis. Supernatants from PMN that had been incub
ated with Candida albicans for 18 h significantly decreased the number
of fresh PMN demonstrating features of apoptosis and increased the pe
rcentage of viable PMN during in vitro culture. This was demonstrated
by monitoring morphologic features of apoptosis with fluorescence micr
oscopy and DNA endonuclease activity with agarose gel electrophoresis,
Significant levels of tumor necrosis factor (TNF) were detectable in
the supernatants of PMN that had been stimulated with C. albicans, as
determined using a TNF-sensitive cell line. Neutralization of TNF biol
ogic activity with a specific monoclonal antibody partially abrogated
the supernatant-mediated prolongation of PMN survival. The present stu
dy demonstrates that PMN possess a mechanism for the modulation of the
ir own survival, which in part may be through the production of TNF.