AUTOCRINE PARACRINE MODULATION OF POLYMORPHONUCLEAR LEUKOCYTE SURVIVAL AFTER EXPOSURE TO CANDIDA-ALBICANS/

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.