title: Polymorphonuclear leukocyte cytoplasts mediate acute lung injury.
abstract: Injection of phorbol 12-myristate 13-acetate (PMA) into polymorphonuclear leukocyte (PMN)-depleted, PMN cytoplast-repleted New Zealand White rabbits caused the development of acute lung injury in vivo. PMN cytoplasts are nucleus- and granule-free vesicles of cytoplasm capable of releasing toxic O2 radicals but incapable of releasing granule enzymes. PMN cytoplasts when activated by PMA reduced 66 +/- 12.7 nmol of cytochrome c compared with 2.6 +/- 0.7 nmol in their resting state and did not release a significant quantity of granule enzymes (P greater than 0.05). Injection of PMA into New Zealand White rabbits caused a significant decrease (P less than 0.05) in the number of circulating cytoplasts. Increases in lung weight-to-body weight ratios in PMA-treated rabbits (9.8 +/- 0.5 X 10(-3] compared with saline-treated rabbits (5.3 +/- 0.2 X 10(-3] were also noted. Levels of angiotensin-converting enzyme in lung lavage as well as the change in alveolar-arterial O2 ratio correlated with the numbers of cytoplasts in lung lavage (P = 0.001, r = 0.84 and P = 0.0166, r = 0.73, respectively). Albumin in lung lavage increased to 1,700 +/- 186 mg/ml in PMA-treated rabbits from 60 +/- 30 mg/ml in saline-treated rabbits. These changes were attenuated by pretreatment of rabbits with dimethylthiourea (DMTU). In vitro, cytoplasts were able to mediate increases in endothelial monolayer permeability. This was evidenced by increases in fractional transit of albumin across endothelial monolayers when treated with PMA-activated cytoplasts (0.08 +/- 0.01 to 0.28 +/- 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Veterans Administration Medical Center, Indianapolis, Indiana.
authors.forename: V B
authors.initials: VB
authors.lastname: Antony
authors.forename: C L
authors.initials: CL
authors.lastname: Owen
authors.forename: D
authors.initials: D
authors.lastname: English
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis / Q000166:cytology / Q000201:enzymology; D002463:Cell Membrane Permeability; D002634:Chemotaxis, Leukocyte; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000503:physiopathology*; D008171:Lung Diseases / Q000209:etiology / Q000503:physiopathology*; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011654:Pulmonary Edema / Q000209:etiology / Q000503:physiopathology; D011817:Rabbits; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D013481:Superoxides; C038983:1,3-dimethylthiourea; D007703:Peptidyl-Dipeptidase A; D013890:Thiourea; D013755:Tetradecanoylphorbol Acetate