Surfactant protein A enhances apoptotic cell uptake and TGF-beta1 release by inflammatory alveolar macrophages.
The phagocytosis of apoptotic inflammatory cells by alveolar macrophages (AMs) is a key component of inflammation resolution within the air space. Surfactant protein A (SP-A) has been shown to stimulate the phagocytosis of apoptotic neutrophils (PMNs) by normal AMs. We hypothesized that SP-A promotes the resolution of alveolar inflammation by enhancing apoptotic PMN phagocytosis and anti-inflammatory cytokine release by inflammatory AMs. Using an LPS lung inflammation model, we determined that SP-A stimulates the phagocytosis of apoptotic PMNs threefold by normal AMs and AMs isolated after LPS injury. Furthermore, SP-A enhances transforming growth factor-beta1 (TGF-beta1) release from both AM populations. Inflammatory AMs release twofold more TGF-beta1 in culture than do normal AMs. SP-A and apoptotic PMNs together stimulate TGF-beta1 release equivalently from normal and inflammatory cultured AMs (330% of unstimulated release by normal AMs). In summary, SP-A enhances apoptotic PMN uptake, stimulates AM TGF-beta1 release, and modulates the amount of TGF-beta1 released when AMs phagocytose apoptotic PMNs. These findings support the hypothesis that SP-A promotes the resolution of alveolar inflammation.
Reidy
Michael F
MF
Box 3709, Duke University Medical Center, Durham, NC 27710, USA.
Wright
Jo Rae
JR
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D037222:Collectins / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D009895:Opsonin Proteins / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D037662:Pulmonary Surfactant-Associated Protein A / Q000494:pharmacology / Q000502:physiology*; D011663:Pulmonary Surfactants / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D037222:Collectins; D008070:Lipopolysaccharides; D009895:Opsonin Proteins; D037662:Pulmonary Surfactant-Associated Protein A; D011663:Pulmonary Surfactants; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1