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Arias-Diaz Javier; Garcia-Verdugo, Ignacio; Casals, Cristina; Sanchez-Rico, Natalia; Vara, Elena; Balibrea, José L.
Clinical Investigations: PDF Only
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ABSTRACT—

Surfactant protein A (SP-A) is thought to play a role in the modulation of lung inflammation during acute respiratory distress syndrome (ARDS). However, SP-A has been reported both to stimulate and to inhibit the proinflammatory activity of pulmonary macrophages (Mφ). Because of the interspecies differences and heterogeneity of Mφ subpopulations used may have influenced previous controversial results, in this study, we investigated the effect of human SP-A on the production of cytokines and other inflammatory mediators by two well-defined subpopulations of human pulmonary Mφ. Surfactant and both alveolar (aMφ) and interstitial (iMφ) macrophages were obtained from multiple organ donor lungs by bronchoalveolar lavage and enzymatic digestion. Donors with either recent history of tobacco smoking, more than 72 h on mechanical ventilation, or any radiological pulmonary infiltrate were discarded. SP-A was purified from isolated surfactant using sequential butanol and octyl glucoside extractions. After 24-h preculture, purified Mφ were cultured for 24 h in the presence or absence of LPS (10 μg/mL), SP-A (50 μg/mL), and combinations. Nitric oxide and carbon monoxide (CO) generation (pmol/μg protein), cell cGMP content (pmol/μg protein), and tumor necrosis factor alpha (TNFα), interleukin (IL)-1, and IL-6 release to the medium (pg/μg protein) were determined. SP-A inhibited the lipopolysaccharide (LPS)-induced TNFα response of both interstitial and alveolar human Mφ, as well as the IL-1 response in iMφ. The SP-A effect on TNFα production could be mediated by a suppression in the LPS-induced increase in intracellular cGMP. In iMφ but not in aMφ, SP-A also inhibited the LPS-induced IL-1 secretion and CO generation. These data lend further credit to a physiological function of SP-A in regulating alveolar host defense and inflammation by suggesting a fundamental role of this apoprotein in limiting excessive proinflammatory cytokine release in pulmonary Mφ during ARDS.

*Department of Surgery, Hospital San Carlos, Madrid, Spain Department of Biochemistry, †Faculty of Biology and ‡Medicine, Complutense University, Madrid, Spain

Presented at the 20th annual meeting of the Surgical Infection Society, April 27-29, 2000, Providence RI.

Address reprint requests to Javier Arias-Diaz, MD, PhD, Departamento de Cirugia Hospital Clinico San Carlos, Ciudad Universitaria, 28040-Madrid, Spain.

Received 28 Apr 2000; first review completed 5 May 2000; accepted in final form 16 Jun 2000

©2000The Shock Society