Doerschuk C M, Kumasaka T, Qin L, Kutkoski G J, Kubo H, Doyle N A, Quinlan W M
Department of Environmental Health Harvard School of Public Health, Boston, MA 02115, USA.
Nihon Kyobu Shikkan Gakkai Zasshi. 1996 Dec;34 Suppl:141-5.
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.
中性粒细胞向肺内的迁移是对间质和肺泡腔中炎症介质的反应。通过肺微血管的迁移通过两条途径发生，一条途径需要CD11/CD18和细胞间黏附分子-1（ICAM-1），另一条则不需要：使用哪条途径取决于刺激因素。刺激因素通过诱导包括肿瘤坏死因子-α（TNF-α）在内的促炎细胞因子的产生来上调ICAM-1的能力，似乎决定了对CD11/CD18、ICAM-1依赖性途径的选择。最近，已确定了第三条途径，该途径需要CD11/CD18，但不需要ICAM-1。这条途径的配体以及CD11/CD18非ICAM-1依赖性黏附的配体尚未确定。在复发性肺炎期间，迁移所需的黏附分子与先前正常肺组织急性炎症期间所利用的黏附分子不同。例如，研究铜绿假单胞菌诱导的复发性肺炎中CD11/CD18的作用，该刺激最初引发CD11/CD18依赖性迁移，结果显示，当在初次接种7天后在同一部位接种该病原体时，大多数迁移通过非CD11/CD18依赖性机制发生。这些研究表明，当急性刺激作用于正在消退的炎症部位时，会募集新的黏附途径。这些分子是否与介导急性非CD11/CD18依赖性黏附的分子相同，仍有待确定。总之，肺内中性粒细胞迁移可通过多种黏附途径发生，在炎症过程中所利用的途径可能会发生变化，并且细胞因子参与途径的选择。
