Related Experiment Videos
Alveolar macrophage response to remote organ injury
J L LaNoue1, J L Iglesias, T E Rogers
1Department of Surgery, University of Texas Southwestern Medical Center at Dallas, 75235-9031, USA.
Abstract:
Intestinal reperfusion (IR)-induced pulmonary edema has been related to endogenous pulmonary thromboxane A2 (TxA2) release. This study examines the hypothesis that alveolar macrophages (aMphis) activated during IR are an important cellular source of TxA2 in this model. Anesthetized Sprague Dawley rats underwent 120 min of intestinal ischemia and 60 min of reperfusion (IR) or sham operation (Sham). aMphis were isolated by bronchoalveolar lavage and incubated in Krebs buffer for 30 min, after which the supernatant was analyzed for TxB2 (metabolite of TxA2) and prostaglandin E2. Other parameters of aMphi activation measured included lysosomal enzyme release (beta-glucuronidase), superoxide (O2-) release, and procoagulant activity. aMphis from animals sustaining IR generated more than twice as much TxA2 and prostaglandin E2 as did those isolated from controls (p < .05). Other evidence of aMphi activation included a nearly 100-fold increase in procoagulant activity, a 7-fold increase in beta-glucuronidase release, and a 2.5-fold increase in O2- release over that of controls (p < .05). These data suggest that TxA2 is a major eicosanoid product of aMphis during IR and that aMphis may be an important cellular participant in IR-induced pulmonary microvascular injury, either directly by releasing O2-, lysosomal enzymes, and pro-coagulant factors, or indirectly by generating TxA2.
Insights
Alveolar macrophages activated during intestinal reperfusion release significant thromboxane A2 (TxA2). These cells also show increased inflammatory markers, suggesting a role in reperfusion injury.
Area of Science:
- Pulmonary Medicine
- Inflammation Research
- Cellular Biology
Background:
- Intestinal reperfusion (IR) can lead to pulmonary edema.
- Endogenous pulmonary thromboxane A2 (TxA2) release is implicated in IR-induced pulmonary edema.
Purpose of the Study:
- To investigate if alveolar macrophages (aMphis) activated during IR are a significant source of TxA2.
- To assess other activation markers of aMphis in the context of IR.
Main Methods:
- Rats underwent intestinal ischemia and reperfusion (IR) or sham operation.
- Alveolar macrophages (aMphis) were isolated via bronchoalveolar lavage.
- TxA2 (as TxB2), prostaglandin E2, lysosomal enzyme release, superoxide release, and procoagulant activity were measured.
Main Results:
- IR-activated aMphis produced over double the amount of TxA2 and prostaglandin E2 compared to controls.
- Procoagulant activity increased nearly 100-fold, beta-glucuronidase 7-fold, and superoxide release 2.5-fold in IR aMphis.
- These findings indicate heightened aMphi activation post-IR.
Conclusions:
- TxA2 is a major eicosanoid product of aMphis during intestinal reperfusion.
- Activated aMphis may contribute to IR-induced pulmonary microvascular injury through direct inflammatory mediator release and indirect TxA2 generation.