Pulmonary Alveolar Macrophage Function during Acute Inflammatory Lung Injury1–3

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Abstract
Pulmonary alveolar macrophages (PAM) are present during acute lung inflammation, yet the functional role of these cells in both the initiation and resolution of lung injury is not well defined. To better understand the relationship between PAM functional responses and the evolution of acute reversible lung injury, we examined the ability of both unstimulated and stimulated (PMA, zymosan) PAM to secrete reactive oxygen metabolites (superoxide anion O−2) and lysosomal enzymes (lysozyme, N-acetyl-b-d-glucosaminidase) at specific time points (0, 6, 12, 24, 48, and 72 h) after initiation of acute lung injury via reverse passive Arthus reaction in pathogen-free Sprague-Dawley rats. After acute lung injury, stimulated PAM produced increasing amounts of O−2 compared with PAM from noninjured lungs. Maximal O−2 production by PAM occurred at 24 h after lung injury, at which time a 3.5-fold and 50% increase in O−2 production by PAM was observed when PAM were stimulated with PMA and zymosan, respectively. The amount of O−2 generated by these cells slowly decreased during the next 48 h. Enhanced generation of O−2 by PAM from injured lungs was not due to altered enzymatic activity of the O−2-producing NADPH oxidase, nor was it due to an absolute increase in the NADPH oxidase in “activated” PAM. These observations suggest that increased O−2 generation by PAM from injured lungs is due to enhancement of mechanisms responsible for induction of oxidase activity. In addition, a differential accumulation and secretion of lysozyme and N-acetyl-b-d-glucosaminidase activity by PAM was observed after acute lung injury. Although basal secretion of N-acetyl-b-d-glucosaminidase by PAM and total cell content of the enzyme were significantly increased in PAM 72 h after lung injury when compared with PAM from noninjured lungs, both the secretion and total cell content of lysozyme were decreased, indicating selective regulation of these 2 enzymes' activities within cells. These observations indicate dynamic regulation of PAM functional responses after acute lung injury and suggest that changes in PAM functional responses may be important in the mediation and resolution of acute inflammatory lung injury.