Complement fragment-induced release of neutrophils from bone marrow and sequestration within pulmonary capillaries in rabbits

Abstract

Infusion of complement fragments induces rapid sequestration of neutrophils within the pulmonary capillaries. This study examined the contributions of the bone marrow (BM) and the liver to the accumulation of neutrophils within the lungs. Complement fragments induced the release of neutrophils from the BM within 7 minutes of infusion, and these neutrophils sequestered in the lungs immediately upon reaching the pulmonary capillaries. Neutrophils expressing high levels of L-selectin were preferentially retained within the pulmonary microvasculature. By 30 minutes after the infusion was stopped, the circulating neutrophil counts had increased, primarily because of release from the BM. The number of neutrophils sequestered in the lung had decreased by only 27%, and the number of neutrophils in the liver increased by 223%. These studies indicate that complement fragments induce the release of neutrophils from the BM far more rapidly than previously described. These newly released neutrophils immediately sequester within the lung, increasing the number of neutrophils available to injure the lung many fold beyond the number that were circulating before infusion. The preferential retention of L-selectin-expressing neutrophils likely reflects the requirement for L-selectin-mediated adhesion in maintaining sequestered neutrophils within the pulmonary microvasculature. The number of circulating neutrophils reflects a balance between pulmonary sequestration, rapid release from the BM, and uptake by the liver and other organs.