Pulmonary Response to Foreign Body Microemboli in Dogs: Release of Neutrophil Chemoattractant Activity by Vascular Endothelial Cells

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Abstract
Pulmonary hypertension and foreign body granulomas are complications of the chronic intravenous injection of crushed, suspended pentazocine (Talwin) tablets. To evaluate the early cellular mechanisms underlying the response of the lung to foreign body microemboli, we examined lung histopathology and bronchoalveolar lavage (BAL) fluid in dogs for accumulation of inflammatory cells shortly after the injection of crushed, suspended pentazocine tablets. We found that the injection of suspended pentazocine tablets is associated with the rapid accumulation of neutrophils around intravascular talc crystals but not within the alveolar airspaces. To determine the cause of the observed neutrophil accumulation, we assayed plasma and lavage fluid for neutrophil chemoattractant activity (NCA). NCA appeared in pulmonary arterial (PA) and left ventricular (LV) plasma within 60 s of injection of the suspended tablets. However, there was no evidence of NCA in BAL. To determine whether appearance of chemoattractant activity found in plasma was modified by inhibitors of arachidonic acid metabolism, we infused dogs with indomethacin, diethylcarbamazine (DEC), or FPL 55712 and assayed plasma for NCA after the injection of suspended pentazocine tablets. We found that the appearance of NCA is prevented by the infusion of either DEC or FPL 55712 but not by the infusion of indomethacin. We found that cultured pulmonary arterial or aortic endothelial cells also release NCA when incubated with either the suspended pentazocine tablets or talc. Extraction with acidified diethyl ether partitioned all the NCA into the organic phase. The release of NCA from cultured endothelial cells was likewise prevented by coincubation with DEC or FPL 55712 but not by coincubation with indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)