HETEROGENOUS AND COMPARTMENT-SPECIFIC ACTIVATION OF NONLYMPHOCYTIC, MONONUCLEAR CELLS IN INTRA-ABDOMINAL SEPSIS

Abstract

Although sepsis is associated with increased production of cellular pro- and anti-inflammatory mediators by monocyte/macrophages, the compartmentalization and nature of such activation has not been clearly defined. The authors examined the activation of nonlymphocytic mononuclear cells in different compartments in the cecal ligation and puncture (CLP) model of septic peritonitis. Control and CLP rat mononuclear cells from the peritoneal cavity, bronchoalveolar, as well as the lung vascular compartment were isolated 24 and 48 hours post surgery and release of nitric oxide (NO), interleukin(IL)-12, and monocyte chemoattractant protein-1 (MCP-1) was measured from culture media. Peritoneal macrophages (PMs) from CLP rats increased release of all three mediators compared to controls. Cells from the lung vascular compartment after CLP increased release of NO, but MCP-1 release was unchanged. Levels of IL-12 were not detectable. Similarly, bronchoalveolar macrophages (BMs) of CLP rats had increased release of NO, whereas IL-12 was not detectable. Release of MCP-1 increased 48 hours after CLP. Almost all PMs and BMs possessed innate phagocytic ability that was not altered during sepsis. The percentage of cells in the lung vascular compartment that had phagocytic ability, increased 48 hours post CLP, versus controls. The authors also evaluated lung injury at 24 hours after surgery by measurement of bronchoalveolar lavage protein and LDH activity. There was an increase in both these parameters 24 hours after CLP as compared to controls. Thus, there was heterogenous and compartment-specific activation of mononuclear cells in sepsis. There was nonspecific inflammatory activation in the primary site of injury. In a remote organ (lung), the authors show for the first time that there was selective activation of NO without increased release of the proinflammatory cytokine, IL-12. Phagocytic activity was maintained in the bronchoalveolar compartment whereas in the lung vascular compartment, the percentage of phagocytic cells increased.