Mechanisms of leukocyte sequestration in inflamed lungs.
The lungs are an important site of host defense. The capillary blood contains an increased concentration of neutrophils and other leukocytes compared with large vessels, due to the structure of the pulmonary capillary bed, the diameter of spherical leukocytes, and their poor deformability compared with erythrocytes. During inflammation within the distal airways, neutrophils sequester within the pulmonary capillaries and emigrate into the parenchyma. This sequential process involves complex events regulating interactions between mechanical and adhesive properties of both neutrophils and endothelial cells. Initial changes in the cytoskeleton may stiffen the neutrophils and prevent them from deforming, while subsequent dynamic cytoskeletal remodeling of neutrophils and endothelial cells results in crawling and transendothelial migration. Emigration of neutrophils can occur through at least two adhesion pathways: one that requires the CD11/CD18 adhesion complex and one that does not. Which pathway is selected is determined by the stimulus and the signaling pathways that are initiated. Migration through the alveolo-capillary wall is also highly regulated. Neutrophils released from the bone marrow traffic first through the pulmonary microvasculature, and the phenotype of these newly released neutrophils impacts pulmonary host defense. The many recent studies underline the complexity of neutrophil responses and host defense and the uncertainties of our knowledge.
Doerschuk
C M
CM
Department of Pediatrics, Case Western Reserve University and University Hospitals Research Institute, Cleveland, OH, USA. cmd22@po.cwru.edu
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D018845:CD11 Antigens / Q000502:physiology; D018821:CD18 Antigens / Q000502:physiology; D002448:Cell Adhesion; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D008168:Lung / Q000473:pathology*; D009504:Neutrophils / Q000502:physiology*; D011014:Pneumonia / Q000473:pathology*
D018845:CD11 Antigens; D018821:CD18 Antigens