Is macrophage-induced microthrombosis during endotoxemia dependent on prostaglandin synthesis?
Steroids and nonsteroidal anti-inflammatory drugs (NSAID), in addition to inhibiting prostaglandin synthesis, have recently been shown to block production of procoagulant activity (PCA) by alveolar macrophages (A-M phi). This inhibition may ameliorate one deleterious effect of endotoxin (LPS), since LPS-induced PCA may contribute to the diffuse microvascular thrombosis (DIC) and subsequent organ failure seen in endotoxemia. However, the results of treatment of endotoxemia with steroids of NSAID are variable or short-lived. To help elucidate the basis for these results, the effect of these agents on production of PCA by another M phi population, the hepatic M phi (H-M phi PCA is functionally discrete from A-M phi PCA) was evaluated. Four agents, (hydrocortisone, indomethacin, ibuprofen and acetylsalicylic acid (ASA)) used to both block production of prostaglandins and ameliorate the deleterious effects of LPS in vivo were tested on the production of rabbit M phi PCA in vitro in homogeneous cultures. PCA was measured by a standardized one-step coagulation assay. Treatment with LPS (1 to 10 g/ml) produced maximal stimulation of PCA production with a peak at 8 hr with PCA levels 20- to 30+-fold higher than controls. The effect of pretreatment (T-10 min) of M phi cultures with the various inhibitors on PCA production at 8 hr post-LPS was evaluated, (N = 6 to 10 experiments).(ABSTRACT TRUNCATED AT 250 WORDS)
Maier
R V
RV
Hahnel
G B
GB
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins / Q000097:blood*; D005938:Glucocorticoids / Q000494:pharmacology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D011453:Prostaglandins / Q000096:biosynthesis*; D011650:Pulmonary Alveoli / Q000166:cytology; D011817:Rabbits; D013927:Thrombosis / Q000097:blood / Q000209:etiology* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D011453:Prostaglandins; D010741:Phospholipases A