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Articles in PresS, published online ahead of print November 2, 2001
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00216.2001
Submitted on June 12, 2001
Accepted on October 15, 2001
1 Anesthesiology, University of Alabama at Birmingham, Birmingham, AL, USA
2 Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
3 Pathobiology and Genomics, University of Alabama at Birmingham, Birmingham, AL, USA
4 Environmental Protection Agency, Research Triangle Park, NC, USA
* To whom correspondence should be addressed. E-mail: sadis.matalon{at}ccc.uab.edu.
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. Co-incubation of AMs with human SP-A (25 µg/ml) and Klebsiella resulted in a 68% decrease in total CFUs by 120 min as compared to 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+]i by 70% and nitrite and nitrate (NOx) production by 45% (from 0.24 ± 0.02 to 1.3 ± 0.21 nmol*106AMs-1*h-1). Preincubation with BAPTA/AM inhibited the increase in intracellular [Ca2+] 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 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.
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