Neutrophil emigration in the lungs.
Neutrophil emigration into the lung occurs in response to inflammatory mediators in the interstitium and the airspace. Emigration through the pulmonary microvasculature occurs through two pathways, one that requires CD11/CD18 and ICAM-1 and one that does not: Which pathway is utilized is determined by the stimulus. The ability of a stimulus to upregulate ICAM-1 by inducing the production of pro-inflammatory cytokines including TNF-alpha appears to determine the selection of the CD11/CD18, ICAM-1, ICAM-1-dependent pathway Recently, a third pathway has been identified that requires CD11/CD18 but not ICAM-1. The ligand for this pathway, as well as the ligands for CD11/CD18, ICAM-1-independent adhesion have not been identified. During recurrent pneumonia, the adhesion molecules required for emigration are different than those utilize during acute inflammation in previously normal lung tissue. For example, studies investigating the role of CD11/CD18 in recurrent pneumonia induced by P. aeruginosa, a stimulus which elicits CD11/CD18-dependent emigration initially, showed that when the organisms are instilled at the same site 7 days after the initial instillation, most emigration occurs through CD11/CD18-independent mechanisms. These studies suggest that when an acute stimulus is placed at a site of resolving inflammation, new pathways of adhesion are recruited. Whether these molecules are the same ones mediating acute CD11/CD18-independent adhesion remains to be determined. In summary, neutrophil emigration in the lung can occur through several adhesion pathways, which pathway is utilized can change during the inflammatory process, and cytokines participate in the selection of the pathway.
Doerschuk
C M
CM
Department of Environmental Health Harvard School of Public Health, Boston, MA 02115, USA.
Kumasaka
T
T
Qin
L
L
Kutkoski
G J
GJ
Kubo
H
H
Doyle
N A
NA
Quinlan
W M
WM
D000818:Animals; D018845:CD11 Antigens / Q000378:metabolism / Q000502:physiology*; D018821:CD18 Antigens / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion; D002465:Cell Movement; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism / Q000502:physiology*; D008168:Lung / Q000166:cytology*; D008171:Lung Diseases / Q000209:etiology; D009504:Neutrophils / Q000502:physiology*
D018845:CD11 Antigens; D018821:CD18 Antigens; D018799:Intercellular Adhesion Molecule-1