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Blockade of Antimicrobial Proteins S100A8 and S100A9 Inhibits Phagocyte Migration to the Alveoli in Streptococcal Pneumonia¹

Centre de Recherche en Infectiologie, Centre de Recherche du Centre Hospitalier de l’Université Laval, and Faculty of Medicine, Laval University, Quebec, Canada

We investigated the roles of the potent, chemotactic antimicrobial proteins S100A8, S100A9, and S100A8/A9 in leukocyte migration in a model of streptococcal pneumonia. We first observed differential secretion of S100A8, S100A9, and S100A8/A9 that preceded neutrophil recruitment. This is partially explained by the expression of S100A8 and S100A9 proteins by pneumocytes in the early phase of Streptococcus pneumoniae infection. Pretreatment of mice with anti-S100A8 and anti-S100A9 Abs, alone or in combination had no effect on bacterial load or mice survival, but caused neutrophil and macrophage recruitment to the alveoli to diminish by 70 and 80%, respectively, without modifying leukocyte blood count, transendothelial migration or neutrophil sequestration in the lung vasculature. These decreases were also associated with a 68% increase of phagocyte accumulation in lung tissue and increased expression of the chemokines CXCL1, CXCL2, and CCL2 in lung tissues and bronchoalveolar lavages. These results show that S100A8 and S100A9 play an important role in leukocyte migration and strongly suggest their involvement in the transepithelial migration of macrophages and neutrophils. They also indicate the importance of antimicrobial proteins, as opposed to classical chemotactic factors such as chemokines, in regulating innate immune responses in the lung.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Canadian Institutes of Health Research Grant 57777 and the Fonds de la Recherche en Santé du Québec (to P.A.T.).

² Address correspondence and reprint requests to Dr. Philippe A. Tessier, Room RC 709, Centre de Recherche du Centre Hospitalier de l’Université Laval, 2705 Boulevard Laurier, Sainte-Foy, Quebec, Canada G1V 4G2. E-mail address: Philippe.Tessier{at}crchul.ulaval.ca

³ Abbreviations used in this paper: BAL, bronchoalveolar lavage; PBST, PBS 0.05% Tween 20.

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