Influence of Short- and Long-Term Endotoxin Administration on the Phagocytic Functions of Polymorphonuclear Leukocytes and Reticuloendothelial System in a Sheep Model

The reticuloendothelial system (RES) is thought to ensure the clearance of embolic particulate matter and blood-borne bacterial substances after trauma, burns, and sepsis [14]. It thereby helps to prevent disturbances to organ integrity, for instance, lung capillary injury, and consequently the development of adult respiratory distress syndrome (ARDS) [1, 7, 11, 25]. In cases of RES blockade, an enhanced deposition of debris and bacterial matter is seen in the lung [13]. It has been suggested that polymorphonuclear leukocytes (PMNLs) then become activated, migrate to the lung, and can take on a major phagocytic role [8, 21]. It is unclear what mechanisms lead to the activation of neutrophils [26] and their pooling in the lung [5]. This is important in that stimulated PMNLs, in addition to substituting for a blocked RES, may lead to pulmonary endothelial damage [14, 16]. The relative injury-producing role of activated PMNLs alone, as opposed to activated PMNLs that have subsequently decompensated, is unknown [15]. It is therefore questionable whether toxic degranulation is a sign of appropriately increased PMNL function or rather a sign of dysfunction. To clarify these issues we used two animal models that would cause acute and chronic lung injury [2] and examined the behavior of the PMNLs and the RES following single and multiple endotoxin bolus injection.