|Kogut, Michael - Mike|
Submitted to: Journal of Immunology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 5/17/2002
Publication Date: 12/1/2002
Citation: Interpretive Summary: When bacteria infect baby chicks, specialized cells in the chicks, called phagocytes, will eat the bacteria. One special type of phagocyte known as the heterophil is very important in the eating and destroying of bacteria in baby chicks. This eating can be improved if the bacteria come in contact with host substances known as antibodies. These antibodies on the bacteria attract the heterophil to the bacteria and increase the ability of the heterophil to eat and destroy the bacteria. The purpose of these experiments was to investigate the chemical reactions that occur inside the heterophil after eating the bacteria that were covered with antibodies. We identified a specific series of reactions that lead to the death of the bacteria. These experiments are important to the pharmaceutical industry because we are now identifying specific natural chemical reactions inside the heterophil that may be targets of drugs to aid in protecting baby chicks from bacterial infections.
Technical Abstract: Originally identified as a T cell growth factor, IL-2 has been found to exercise an array of biological effects on other cell types. Of particular interest is the ability of IL-2 to activate microbicidal and tumoricidal activities in cells of the innate immune response. The recent cloning and sequencing of the avian IL-2 homologue has speculated on its use as either a vaccine adjuvant or immunomodulator molecule in poultry. Heterophils, th avian equivalent of the neutrophil, function as professional phagocytes to aid in regulation of innate host defenses. The objective of the present studies was to examine the effects of recombinant chicken IL-2 (rChIL-2) on various functional activities of heterophils from chickens during the first three weeks after hatch. Peripheral blood heterophils were isolated and incubated with various concentrations of either COS cell-derived rChIL-2 or supernatants from mock-transfected COS cells for 2 h at 39 deg C. RChIL-2 had no effect on the functional activities of heterophils from day-of-hatc chickens. However, rChIL-2 significantly increased the phagocytosis and bactericidal activity of heterophils from 7- and 14-day-old chickens. RChIL-2 induced no direct stimulation of the respiratory burst by heterophils from birds at any age, but primed heterophils from 7- and 14- day-old birds for a significantly strengthened respiratory burst to subsequent stimulation with PMA. Lastly, rChIL-2 had neither direct nor priming effects on heterophil degranulation. The effects on heterophil functional activity were neutralized by a neutralizing anti-chicken IL-2 mAb and were therefore specific. These results show that rChIL-2 can directly activate chicken heterophils to exert effector functions, and that heterophil activation by rChIL-2 is also an age-dependent event.