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

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.

Serglycin: A Structural and Functional Chameleon with Wide Impact on Immune Cells

“…An observation in line with these findings is that aging serglycin 2/2 mice spontaneously develop a massive enlargement of multiple lymphoid tissues, including spleen, BALT, and Peyer's patches (60), suggesting that serglycin has functions in maintaining homeostasis of the body's immune cell populations, for example, through effects on proliferation, apoptosis, or both.…”

A Role for Serglycin Proteoglycan in Mast Cell Apoptosis Induced by a Secretory Granule-mediated Pathway

“…It has recently been demonstrated that animals lacking SG spontaneously develop an enlargement of multiple lymphoid tissues/organs (11) and a markedly delayed contraction of the CD8 ϩ T cell response following virus infection (12). Although multiple explanations for these findings may apply, one possibility would be that the absence of SG affects the ability of certain leukocyte populations to undergo apoptosis.…”

Serglycin-independent Release of Active Mast Cell Proteases in Response to Toxoplasma gondii Infection

“…Flow Cytometry-Peritoneal cells (0.5 ϫ 10 6 ) were stained with a PE-conjugated CD117-specific antibody or with an isotype-matched control antibody (Immunotools, Friesoythe, Germany) as described (29) and counted on a Beckman Coulter flow cytometer.…”

“…Moreover, MC proteases possibly provide a soluble link between the innate and adaptive immunity in vivo, as demonstrated by the reduced adaptive response of mMCP-4-deficient mice in experimental arthritis (27) and by the inability of mMCP-6 deficient mice to recruit eosinophils to skeletal muscle tissue in response to infection with Trichinella spiralis larvae (28). We recently reported that SG deficiency results in several age-dependent alterations in the lymphoid system of naïve mice, possibly as a result of the impaired storage of potent inflammatory mediators within secretory granules (29). However, the importance of SGPGs for regulation of MC proteases in different inflammatory reactions is only partly understood.…”