Inflammatory events after fibrin microembolization. Alterations in alveolar macrophage and neutrophil function.
We performed bronchoalveolar lavage (BAL) 0.5 to 24 h after thrombin-induced pulmonary microembolization in spontaneously breathing sheep to examine the inflammatory events that occur after pulmonary intravascular coagulation. Neutrophil alveolitis was evident as early as 0.5 h after microembolization and was maximal at 4 h (4.9 +/- 1.5% neutrophils of total BAL cells at baseline versus 26.2 +/- 2.8% at 4 h post-thrombin). Neutrophils obtained both at baseline (isolated from peripheral blood) and at 0.5 to 24 h after thrombin (isolated from BAL) did not demonstrate significant basal production of superoxide anion (O2-) and produced similar amounts of O2- upon challenge with phorbol myristate acetate (PMA) 200 micrograms/ml. The basal O2- production by alveolar macrophages was also not increased. However, alveolar macrophages recovered after fibrin microembolization produced greater amounts of O2- (29.1 +/- 6.3 nm O2-/10(6) cells at 0.5 h) after challenge with PMA compared with alveolar macrophages recovered prior to embolization (10.6 +/- 1.6 nm O2-/10(6) cells baseline), suggesting that thrombin-induced microembolization primes alveolar macrophages and enhances their O2- generation. Neutrophil chemotactic activity was detected in BAL fluid at 0.5 h post-microembolization and reached a peak level at 2 h. Alveolar macrophages were a source of the chemotactic activity since conditioned medium obtained from 2-h post-thrombin macrophages induced neutrophil chemotaxis, whereas baseline cells did not. The addition of the thrombin to macrophages did not result in the generation of chemotactic activity from baseline macrophages, indicating that macrophages were activated during the process of intravascular coagulation rather than by thrombin per se. Post-thrombin BAL fluid also stimulated O2- generation from sheep neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)
Garcia
J G
JG
Department of Physiology, Albany Medical College, Union University, NY12208.
Perlman
M B
MB
Ferro
T J
TJ
Johnson
A
A
Jubiz
W
W
Malik
A B
AB
D000418:Albumins / Q000032:analysis; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis / Q000166:cytology*; D002452:Cell Count; D005337:Fibrin; D008264:Macrophages / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D011014:Pneumonia / Q000097:blood / Q000209:etiology / Q000473:pathology*; D011655:Pulmonary Embolism / Q000097:blood / Q000209:etiology / Q000473:pathology*; D012756:Sheep; D013481:Superoxides / Q000032:analysis
D000418:Albumins; D013481:Superoxides; D005337:Fibrin