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Blood, 15 October 2005, Vol. 106, No. 8, pp. 2871-2878. Prepublished online as a Blood First Edition Paper on July 5, 2005; DOI 10.1182/blood-2005-04-1522.
Submitted April 14, 2005
Metschnikoff, Max-Planck-Institut fur Immunbiologie, Freiburg, Germany * Corresponding author; email: simon{at}immunbio.mpg.de.
Polymorphonuclear leukocytes have been shown to employ a multitude of effector functions to combat pathogens and tumors, including enzymes, defensins, and toxic products such as oxygen radicals and nitrogen oxides. Recent studies provided evidence for the expression of granzymes (gzm) and perforin (perf) within the cytotoxic arsenal of human neutrophils, the validity of which was questioned by two subsequent studies. We have now employed cytology, intracellular flow cytometry, enzymatic assays, immunoelectron microscopy and quantitative reverse transcriptase-polymerase chain reaction to obtain evidence of the presence of gzms and/or perf in mouse Gr-1+ granulocyte populations. The data obtained clearly demonstrate that neither in vitro nor in vivo-derived mouse granulocytes synthesize gzmA and gzmB or perf, even following infection/immunization with pathogens or pathogen-derived material. A parallel comparable analysis on the expression of gzmB in human neutrophils from three normal controls and four patients with diverse diseases failed to detect gzmB expression. The data indicate that polymorphonuclear leukocytes from mouse and man lack the three cytotoxic effector molecules, gzmA, gzmB and perf, generally associated with natural killer and cytotoxic T lymphocytes.
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