Submitted to: Journal of Inflammation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 28, 2000
Publication Date: January 5, 2001
Interpretive Summary: Studies from our laboratory have shown that products (lymphokines) released by a type of white blood cell (the T lymphocyte) can stimulate a second type of white blood cell called the heterophil. Heterophils function by eating and destroying foreign objects, including pathogenic bacteria like Salmonella, that invade the body of a baby chicken. The objective of this experiment was to test the ability of a specific type of lymphokine known as interferon-gamma to stimulate the eating and killing functions of heterophils from baby chickens. The results showed that the heterophils treated with interferon-gamma were able to eat and kill more bacteria then the heterophils that were not treated with interferon-gamma. These results are important because we now know of a specific lymphokine that can stimulate one part of the baby chicken's immune system. This kind of treatment should make the baby chicken able to fight bacterial infections early in life.
Technical Abstract: The activation of signal transduction pathways is required for the expression of functional enhancement of cellular activities. In the present studies, initial attempts were made to identify the signal transduction factors involved in activating functional activities by chicken heterophils isolated in response to opsonized Salmonella enteritidis (opsonized SE). Peripheral blood heterophils were exposed to known inhibitors of signal transduction pathways for either 20 min (staurosporin, genistein, or verapamil) or 120 min (pertussis toxin). The cells were then stimulated for 30 min with opsonized SE. The G-protein inhibitor pertussis toxin markedly inhibited (> 80%) phagocytosis of opsonized SE. Both the protein kinase inhibitor (staurosporin) and calcium channel inhibitor (verapamil) reduced phagocytosis in a dose responsive manner. Staurosporin had a marked inhibitory effect on LDCL (> 90%) while genistein had a dose responsive inhibition on LDCL. Both verapamil (40-45%) and pertussis toxin (50-55%) had a statistically significant effect on LDCL. Genistein (78-81%) and staurosporin (43-50%) significantly reduced the degranulation of heterophils by opsonized SE. These findings demonstrate that distinct signal transduction pathways differentially regulate the stimulation of the functional activities of avian heterophils. Pertussis toxin-sensitive, Ca++-dependent G-proteins appear to regulate phagocytosis of opsonized SE, protein kinase C- dependent, tyrosine kinase-dependent protein phosphorylation plays a major role in LDCL, and tyrosine kinase (s)-dependent phosphorylation regulates primary granule release.