Neutrophil depletion inhibits early and late monocyte/macrophage increase in lung inflammation

Monocytes/macrophages have critical impact on outcomes of lung inflammation. Kinetics and mechanisms for the increase of monocytes/macrophages in lungs are not completely understood. To better understand these mechanisms, E. coli-LPS (250 micro grams; N = 35) or endotoxin-free saline ( N = 5) were instilled intratracheally in Sprague-Dawley rats and the increase in monocytes/macrophages, neutrophils and monocyte chemotactic protein-1 (MCP-1) was quantified at various time points after LPS treatment. In contrast to typical pattern of neutrophil influx between 6 and 24 hours, monocytes/macrophages increased in two distinct phases, very early at 3 hours and late at 24 hours. The role of neutrophils in monocyte/macrophage increase was addressed in LPS-challenged neutropenic rats (N=8). Neutrophil depletion before instillation of LPS abrogated the early as well as late monocyte/macrophage increases in the lung. Quantification of MCP-1, which is one of the major chemoattractants for monocytes, in lung homogenates showed similar concentrations in neutropenic and non-neutropenic LPS-challenged rats. These findings show that increase in monocytes/macrophages in lung occurs in two, early and late phases, both being dependent on neutrophils but not on MCP-1.