Abstract
During early inflammation, the chemoattractants neutrophil-activating peptide-2 (NAP-2), platelet-activating factor (PAF), and complement component C5a are rapidly generated within the vasculature and potently induce effector functions in neutrophils, such as chemotaxis and degranulation. We investigated whether these mediators would cross-desensitize each other's activities on isolated neutrophils. We demonstrate that NAP-2 and C5a desensitize degranulation of neutrophils in response to PAF. However, whereas C5a-mediated desensitization correlated with the downregulation of PAF binding sites on neutrophils, NAP-2 did not regulate PAF receptors, nor did it modulate their calcium signaling. In further contrast to C5a, which desensitized PAF-induced neutrophil chemotaxis, NAP-2 did not affect the chemotatic response to PAF. These observations indicate that NAP-2 mediates selective desensitization of PAF-induced neutrophil degranulation by a mechanism downstream from PAF receptors, still allowing migration toward PAF. Thus, a role for NAP-2 may be to limit PAF-dependent vascular tissue damage by preventing degranulation of neutrophils without affecting their migration into the inflamed tissue.
References
Nov 15, 1992·The Biochemical Journal·J T O'FlahertyJ F Redman
Dec 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·J R DidsburyR Snyderman
Jan 24, 1991·Nature·Z HondaT Miyamoto
Jul 1, 1991·Cytokine·E BrandtH D Flad
Oct 15, 1991·Biochemical and Biophysical Research Communications·W SchnitzelJ Besemer
Dec 1, 1989·Molecular Immunology·W VogtD Brunahl
Nov 1, 1989·The Journal of Experimental Medicine·A WalzM Baggiolini
Dec 16, 1987·Biochemical and Biophysical Research Communications·A WalzM Baggiolini
Dec 1, 1983·Inflammation·H R CreamerW W Bullock
Jun 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·E MüllerM Rola-Pleszczynski
Nov 8, 1996·The Journal of Biological Chemistry·R M RichardsonR Snyderman
Nov 1, 1996·Trends in Pharmacological Sciences·T T ChuangA De Blasi
Mar 21, 1998·Cellular Signalling·E J Pettit, M B Hallett
May 23, 1998·The Journal of Biological Chemistry·I IshiiT Shimizu
May 30, 1998·The Journal of Biological Chemistry·R M RichardsonR Snyderman
Jun 6, 1998·The Journal of Biological Chemistry·H AliR Snyderman
Sep 3, 1998·The Journal of Biological Chemistry·R M RichardsonR Snyderman
Feb 26, 1999·The Journal of Biological Chemistry·H AliR Snyderman
Jan 4, 2001·Immunological Reviews·E BrandtH D Flad
Citations
Jul 27, 2007·Artificial Organs·Ann Elisabeth Asberg, Vibeke Videm
Dec 23, 2011·Molecular Immunology·Kyoung-Soon JangSeung Hyun Han
Nov 3, 2015·PloS One·Christian ErbelChristian A Gleissner
May 16, 2015·PloS One·Christoph EhlkenAmelie Pielen
Jul 22, 2016·PloS One·Yvonne FörsterStefan Rammelt
Nov 9, 2004·The Journal of Biological Chemistry·Irina V NesmelovaKevin H Mayo
Apr 12, 2014·Oncotarget·Manuel Puig-CostaJavier A Menendez
Jun 3, 2021·Brain Research Bulletin·Junrui YeNaihong Chen