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Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo, Japan;
Department of Biochemistry, Kyushu University School of Medicine, Fukuoka, Japan; and
Lord and Tayler Laboratory for Lung Biochemistry, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206
Pulmonary surfactant protein A (SP-A) plays an important part in
Ab-independent host defense mechanisms of the lung. In this study we
investigated how SP-A interacts with distinct serotypes of bacterial
LPS and modulates LPS-elicited cellular responses. SP-A bound to rough
forms but not to smooth forms of LPS. In the macrophage-like cell line
U937, SP-A inhibited mRNA expression and secretion of TNF-
induced
by smooth LPS, but rough LPS-induced TNF-
expression was unaffected
by SP-A. When U937 cells and rat alveolar macrophages were preincubated
with SP-A, smooth LPS failed to induce TNF-
secretion, whereas rough
LPS-induced TNF-
secretion was modestly increased. To clarify the
mechanism by which SP-A modulates LPS-elicited cellular responses, we
further examined the interaction of SP-A with CD14, which is known as a
major LPS receptor. Western blot analysis revealed that CD14 was one of
the SP-A binding proteins isolated from solubilized U937 cells. In
addition, SP-A directly bound to recombinant soluble CD14 (rsCD14).
When rsCD14 was preincubated with SP-A, the binding of rsCD14 to smooth
LPS was significantly reduced but the association of rsCD14 with rough
LPS was augmented. These results demonstrate the different actions of
SP-A upon distinct serotypes of LPS and indicate that the direct
interaction of SP-A with CD14 constitutes a likely mechanism by which
SP-A modulates LPS-elicited cellular responses.
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