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Originally published online as doi:10.1189/jlb.1008670 on December 16, 2008

Published online before print December 16, 2008
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(Journal of Leukocyte Biology. 2009;85:401-408.)
© 2009 by Society for Leukocyte Biology

Age-related enlargement of lymphoid tissue and altered leukocyte composition in serglycin-deficient mice

Sara Wernersson*, Tiago Braga*,1, Osama Sawesi*,1, Ida Waern*,1, Kajsa E. Nilsson{dagger}, Gunnar Pejler*,2 and Magnus Åbrink{ddagger},2

* Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry, Uppsala, Sweden; and Departments of
{dagger} Cell and Molecular Biology and
{ddagger} Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden

2 Correspondence: Swedish University of Agricultural Sciences, Dept. of Anatomy, Physiology and Biochemistry, BMC, Box 575, 75123 Uppsala, Sweden. E-mail: gunnar.pejler{at}afb.slu.se. Uppsala University, Dept. of Medical Biochemistry and Microbiology, BMC, Box 582, 75123 Uppsala, Sweden. E-mail: magnus.abrink{at}imbim.uu.se

ABSTRACT

Serglycin (SG) is a proteoglycan that is located predominantly in the secretory granules of hematopoietic cells. Previous studies have established a crucial role for SG in promoting the storage of various secretory granule compounds that are of importance in the immune defense system. Here, we show that mice lacking SG spontaneously develop enlargement of multiple lymphoid organs, including the spleen, Peyer’s patches (PP), and bronchus-associated lymphoid tissue. In the spleen, the lack of SG resulted in a significant decrease in the proportion of CD4+ cells as well as an increase of the CD45RC+ leukocyte population, indicating an expansion of naïve lymphocytes. In the PP, the lack of SG resulted in a general increase in cellularity, without significant alterations in the proportion of individual leukocyte populations. The enlargement of lymphoid tissues was not accompanied by increased serum levels of inflammatory cytokines. The number of mast cells in the peritoneum was not affected by the lack of SG, as judged by surface staining for CD117 (c-kit). However, the intensity of c-kit staining was reduced significantly in SG null animals. Moreover, the number of peritoneal macrophages, defined by morphological criteria and by CD11b staining, was decreased markedly in older, SG-deficient animals. Finally, experiments in which airway inflammation was induced by bacterial LPS revealed a more pronounced inflammatory response in old, SG-deficient as compared with wild-type mice. Taken together, our data show that SG deficiency causes multiple, age-related effects on the lymphoid system.

Key Words: proteoglycans • mast cells • macrophages • CD45RC • BALT • CD11b