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Monocyte and Macrophage Activation by Lipoteichoic Acid Is Independent of Alanine and Is Potentiated by Hemoglobin¹

David L. Hasty^2,*,, Shiri Meron-Sudai^¶, Kathleen H. Cox, Tetyana Nagorna, Eduardo Ruiz-Bustos^3,, Elena Losi^4,, Harry S. Courtney^*,, Engy A. Mahrous, Richard Lee and Itzhak Ofek^¶

^* Research Service (151), Department of Veterans Affairs Medical Center, Memphis, TN, 38104; Departments of Anatomy and Neurobiology, Department of Medicine, and Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163; and ^¶ Department of Human Microbiology, Tel Aviv University, Tel Aviv, Israel

Lipoteichoic acids (LTAs) are Gram-positive bacterial cell wall components that elicit mononuclear cell cytokine secretion. Cytokine-stimulating activity is thought to be dependent on retaining a high level of ester-linked D-alanine residues along the polyglycerol phosphate backbone. However, Streptococcus pyogenes LTA essentially devoid of D-alanine caused human and mouse cells to secrete as much IL-6 as LTA with a much higher D-alanine content. Furthermore, hemoglobin (Hb) markedly potentiates the stimulatory effect of various LTAs on mouse macrophages or human blood cells, regardless of their D-alanine content. LTA and Hb appear to form a molecular complex, based on the ability of each to affect the other’s migration on native acrylamide gels, their comigration on these gels, and the ability of LTA to alter the absorption spectra of Hb. Because S. pyogenes is known to release LTA and secrete at least two potent hemolytic toxins, LTA-Hb interactions could occur during streptococcal infections and might result in a profound alteration of the local inflammatory response.

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