Dynamic changes in neutrophil defensins during endotoxemia.
Bacterial endotoxin or lipopolysaccharide (LPS) is an important causative agent of sepsis. This study determines the expression of defensins NP-2 and NP-5 and the function of polymorphonuclear leukocytes (PMN) in rabbits treated with LPS. PMN functional activity was assessed by measuring CD18 expression and H(2)O(2) production and by examining the lungs. NP-2 and, to a minor extent, NP-5 of circulating PMN increase during endotoxemia. This early increase is concomitant with neutrophilia and elevated CD18 expression and H(2)O(2) production, as well as with enhanced NP-2 immunoreactivity in pulmonary microvessels. A decline in defensins, shortly after the last LPS treatment, is associated with a decrease in the circulating activated PMN and enhanced immunoreactivity in the inflammatory cells, as well as with lung tissue damage. This study shows that LPS-induced changes in the defensins of circulating PMN correlate with the number and activated condition of these cells and suggests that PMN-derived products implement the inflammatory reaction that leads to lung injury and sepsis.
Klut
M E
ME
University of British Columbia McDonald Research Laboratories, iCAPTURE Centre, St. Paul's Hospital, Vancouver, British Columbia, Canada. Mklut@mrl.ubc.ca
Whalen
B A
BA
Hogg
J C
JC
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001775:Blood Circulation; D018821:CD18 Antigens / Q000096:biosynthesis; D054412:Chemokine CCL8; D023082:Defensins / Q000096:biosynthesis*; D019446:Endotoxemia / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology*; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D008168:Lung / Q000473:pathology; D018945:Monocyte Chemoattractant Proteins / Q000096:biosynthesis; D009504:Neutrophils / Q000276:immunology*; D011817:Rabbits
D000900:Anti-Bacterial Agents; D018821:CD18 Antigens; D054412:Chemokine CCL8; D023082:Defensins; D018945:Monocyte Chemoattractant Proteins; D006861:Hydrogen Peroxide