Nitric oxide reduces the sequestration of polymorphonuclear leukocytes in lung by changing deformability and CD18 expression.
Nitric oxide (NO) influences polymorphonuclear leukocytes (PMN)-endothelial cell interactions. The aim of this study was to evaluate this effect in the lung and investigate this mechanism. PMN sequestration in the lung was evaluated in vivo after the infusion of complement fragments. Rabbits (n = 9) that inhaled 40 ppm of NO were compared with control rabbits (n = 9) over a 2-h period following infusion of complement fragments. Circulating PMN counts immediately decreased after infusion of complement fragments in both groups followed by a recovery to baseline. This recovery was maintained in the NO-treated group compared with the control rabbits (p < 0.05). NO reduced PMN sequestration in the lung measured by both arteriovenous PMN difference across the lung (p < 0.01) and the myeloperoxidase (MPO) content of the lung tissue (p < 0.01). NO had no effect on the complement fragments-induced PMN release from the bone marrow. In vitro studies showed that NO partially inhibited F-actin assembly (p < 0.01) reduced the change in deformability (p < 0.05) and inhibited CD18 upregulation (p < 0.05) but had no effect on the L-selectin shedding of PMN stimulated by complement fragments. We conclude that NO reduces the sequestration of activated PMN by reducing deformability change via inhibition of F-actin assembly and inhibiting the upregulation of CD18.
Sato
Y
Y
University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, British Columbia, Canada.
Walley
K R
KR
Klut
M E
ME
English
D
D
D'yachkova
Y
Y
Hogg
J C
JC
van Eeden
S F
SF
D000199:Actins / Q000378:metabolism; D000818:Animals; D001158:Arteries; D001854:Bone Marrow Cells / Q000502:physiology; D018821:CD18 Antigens / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D005260:Female; D007958:Leukocyte Count / Q000187:drug effects; D008168:Lung / Q000166:cytology* / Q000201:enzymology; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D014680:Veins
D000199:Actins; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D009569:Nitric Oxide; D009195:Peroxidase