Alveolocapillary Cross-Talk: Giles F. Filley Lecture

Abstract

Host defense mechanisms fall in the categories of innate and adaptive immunity. The innate immune system deploys rapid-defense mechanisms, while the adaptive immune system activates a slower antigen-specific defense. In pulmonary alveoli that are continually exposed to airborne antigens, innate immune mechanisms are well developed and rapidly instituted. A large number of pathogenic substances including viruses, bacteria, and lipopolysaccharide, when introduced in the airway, induce leukocyte migration into the alveolus within 3 to 4 h, attesting to the efficacy of alveolar innate immunity. 1 Skerrett SJ Martin TR Chi EY et al. Role of the type 1 TNF receptor in lung inflammation after inhalation of endotoxin orPseudomonas aeruginosa. Am J Physiol. 1999; 276: L715-L727 PubMed Google Scholar This time course is consistent with secretion of chemokines such as tumor necrosis factor (TNF)-α from alveolar macrophages, which provide the chemotactic signal for leukocyte recruitment. Ample evidence attests to this chemotactic effect, in that chemokines either directly instilled in the airspace or released on secretion by alveolar macrophages 1 Skerrett SJ Martin TR Chi EY et al. Role of the type 1 TNF receptor in lung inflammation after inhalation of endotoxin orPseudomonas aeruginosa. Am J Physiol. 1999; 276: L715-L727 PubMed Google Scholar , 2 Koh Y Hybertson BM Jepson EK et al. Tumor necrosis factor-induced acute lung leak in rats: less than with interleukin-1. Inflammation. 1996; 20: 461-469 Crossref PubMed Scopus (27) Google Scholar , 3 Lukacs NW Strieter RM Chensue SW et al. TNF-α mediates recruitment of neutrophils and eosinophils during airway inflammation. J Immunol. 1995; 154: 5411-5417 PubMed Google Scholar induce leukocyte influx into alveoli. It is clear that the chemotactic signal must vectorially cross the alveolar barrier to the site of leukocyte recruitment in adjoining capillaries. However, little attention has been paid to the role played by the alveolar wall epithelium in this inflammatory process.