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Reticuloendothelial clearance of blood-borne particulates: relevance to experimental lung microembolization and
Abstract:
The rapid increase in sheep lung vascular permeability observed during Pseudomonas aeruginosa bacteremia may be due to embolization of the pulmonary microvasculature by bloodborne particulates. Since alterations in lung microvascular permeability during mild septicemia in sheep may reflect inefficient RES phagocytic clearance of bacteria as well as products of bacterial induced intravascular coagulation, the opsonic and phagocytic aspects of RES function in sheep (30-50 kg) were compared to other species. RES function was evaluated by both the clearance and relative organ uptake of gelatinized I(131) RE test lipid emulsion and gelatinized colloidal carbon. Immunoreactive opsonic a(2)SB glycoprotein levels were determined by electroimmunoassay. The phagocytic index for RES clearance of the gelatinized (500 mg/kg) test lipid in sheep was 0.019 +/- 0.002 corresponding to a half-time of 16.65 +/- 1.74 minutes. With colloidal carbon (64 mg/kg), the phagocytic index in sheep was 0.080 +/- 0.026, corresponding to a half-time of 6.16 +/- 1.99 minutes. The per cent of injected lipid emulsion (%ID) in major RE organs, on a total organ basis (TO), was: liver = 15.69 +/- 1.65%; spleen = 2.09 +/- 0.78%. Localization in the lung = 31.39 +/- 6.2%. The per cent of carbon localized in major RE organs (%ID/TO) was: liver = 21.37 +/- 1.9%; spleen = 1.95 +/- 0.55%. Localization in the lung = 32.70 +/- 4.55%. In contrast, clearance and organ distribution of the blood-borne test microparticles in rats and dogs at the same relative challenging dose revealed a much more intense and rapid liver and spleen RES uptake with minimal lung localization (1-2%). Immunoreactive opsonic protein concentrations varied greatly with species and directly correlated with efficiency of RES function. Levels observed were: dog = 1285 +/- 135 microg/ml; mouse = 1077 +/- 67 microg/ml; rat = 400 +/- 31 microg/ml; human = 297 +/- 10 microg/ml; and sheep = 184 +/- 13 microg/ml. After intravenous particulate challenge, circulating immunoreactive opsonic protein in the sheep was depleted (p < 0.05) rapidly with partial recovery at 24 hours and mild rebound hyperopsonemia at 48 hours. This pattern is in contrast to the rapid restoration seen in dog and rat within three to six hours postchallenge. Thus, in sheep, the extensive pulmonary localization of blood-borne microparticles appears related to inefficient RES clearance function mediated by a relative deficiency of circulating opsonic protein (plasma fibronectin).
Insights
Sheep exhibit inefficient RES function and low opsonic protein levels, leading to extensive pulmonary microparticle localization during bacteremia. This contrasts with more efficient clearance observed in other species like dogs and rats.
Area of Science:
- Immunology
- Physiology
- Comparative Medicine
Background:
- Pulmonary vascular permeability increases in sheep during Pseudomonas aeruginosa bacteremia, potentially due to microvascular embolization by bloodborne particulates.
- Inefficient reticuloendothelial system (RES) phagocytic clearance of bacteria and intravascular coagulation products may contribute to altered lung microvascular permeability during septicemia.
Purpose of the Study:
- To compare the opsonic and phagocytic aspects of RES function in sheep with other species.
- To investigate the relationship between RES function, opsonic protein levels, and microparticle localization in the lungs.
Main Methods:
- RES function was evaluated using clearance and organ uptake of gelatinized I(131) RE test lipid emulsion and colloidal carbon in sheep, rats, and dogs.
- Immunoreactive opsonic α2SB glycoprotein levels were quantified using electroimmunoassay.
- Changes in circulating opsonic protein were monitored post-intravenous particulate challenge.
Main Results:
- Sheep demonstrated significantly higher pulmonary localization (31-32%) of test microparticles compared to rats and dogs (1-2%).
- Sheep exhibited lower phagocytic indices and slower clearance rates for both lipid emulsion and colloidal carbon.
- Sheep had markedly lower circulating immunoreactive opsonic protein levels (184 μg/ml) compared to dogs (1285 μg/ml) and rats (400 μg/ml), with rapid depletion post-challenge.
Conclusions:
- The extensive pulmonary localization of blood-borne microparticles in sheep is linked to inefficient RES clearance.
- This inefficiency is mediated by a relative deficiency in circulating opsonic protein, identified as plasma fibronectin.
- Species-specific differences in RES function and opsonic protein levels are critical in managing particulate clearance during septicemic conditions.