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Am J Physiol Lung Cell Mol Physiol 282: L944-L956, 2002. First published November 2, 2001; doi:10.1152/ajplung.00216.2001
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Vol. 282, Issue 5, L944-L956, May 2002

EDITORIAL FOCUS
Killing of Klebsiella pneumoniae by human alveolar macrophages

Judy M. Hickman-Davis1, Philip O'Reilly2, Ian C. Davis3, Janos Peti-Peterdi4, Glenda Davis1, K. Randall Young2, Robert B. Devlin5, and Sadis Matalon1,3,6

Division of Pulmonary and Critical Care Medicine, Departments of 1 Anesthesiology and 2 Medicine, Division of Nephrology and Nephrology Research Training Center, Departments of 3 Genomics and Pathobiology and 4 Medicine, 6 Department of Physiology and Biophysics, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294; and 5 Environmental Protection Agency, Research Triangle Park, North Carolina 27711-0001

We investigated putative mechanisms by which human surfactant protein A (SP-A) effects killing of Klebsiella pneumoniae by human alveolar macrophages (AMs) isolated from bronchoalveolar lavagates of patients with transplanted lungs. Coincubation of AMs with human SP-A (25 µg/ml) and Klebsiella resulted in a 68% decrease in total colony forming units by 120 min compared with AMs infected with Klebsiella in the absence of SP-A, and this SP-A-mediated effect was abolished by preincubation with NG-monomethyl-L-arginine. Incubation of transplant AMs with SP-A increased intracellular Ca2+ concentration ([Ca2+]i) by 70% and nitrite and nitrate (NOx) production by 45% (from 0.24 ± 0.02 to 1.3 ± 0.21 nmol · 106 AMs-1 · h-1). Preincubation with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester inhibited the increase in [Ca2+]i and abrogated the SP-A-mediated Klebsiella phagocytosis and killing. In contrast, incubation of AMs from normal volunteers with SP-A decreased both [Ca2+]i and NOx production and did not result in killing of Klebsiella. Significant killing of Klebsiella was also seen in a cell-free system by sustained production of peroxynitrite (>1 µM/min) at pH 5 but not at pH 7.4. These findings indicate that SP-A mediates pathogen killing by AMs from transplant lungs by stimulating phagocytosis and production of reactive oxygen-nitrogen intermediates.

innate immunity; collectins; peroxynitrite; lung transplant; phagolysosome


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